UTX (gene)

Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), is a protein which in humans is encoded by the "KDM6A" gene. It belongs to the 2-oxoglutarate (2OG)-dependent dioxygenase superfamily.
Function.
UTX has been linked with demethylation of lysine residues on histone, in particular H3K27, resulting in a gene de-repression, a potential means of regulating cellular metabolism.


HUH-tag

HUH endonucleases (HUH-tags) are sequence-specific single-stranded DNA (ssDNA) binding proteins originating from numerous species of bacteria and viruses. Viral HUH endonucleases are involved in initiating rolling circle replication while ones of bacterial origin initiate bacterial conjugation. In biotechnology, they can be used to create protein-DNA linkages, akin to other methods such as SNAP-tag. In doing so, they create a 5' covalent bond between the ssDNA and the protein. HUH endonucleases can be fused with other proteins or used as protein tags.
Types of HUH endonucleases.
HUH endonucleases are broadly split into two categories of enzymes: replication initiator proteins (Rep) or relaxase / mobilization proteins. They both contain small protein domains that recognize sequence-specific origins of replication or origin of transfer at which site they nick DNA. The nicking domain of Reps tend to be smaller, on the order of 10-20 kDa while nicking domains from relaxases are larger, roughly 20-40 kDa in size.
Mode of action.
HUH endonucleases generally have two histidine (H) residues in the active site coordinating a metal cation (Mg2+ or Mn2+) that interacts with the phosphate backbone of DNA. This allows for a nucleophilic attack, most commonly, by an activated tyrosine of the scissile phosphate in the DNA backbone, generating a 5' covalent bond with the ssDNA. In contrast to other DNA-protein linkage approaches, this reaction occurs at ambient conditions and does not require any additional modifications. X-ray crystallography and NMR structures have provided insight into the sequence specificity of DNA binding.


BED zinc finger

In molecular biology the BED-type zinc finger domain is a protein domain which was named after the Drosophila proteins BEAF and DREF, is found in one or more copies in cellular regulatory factors and transposases from plants, animals and fungi. The BED finger is an about 50 to 60 amino acid residues domain that contains a characteristic motif with two highly conserved aromatic positions, as well as a shared pattern of cysteines and histidines that is predicted to form a zinc finger. As diverse BED fingers are able to bind DNA, it has been suggested that DNA-binding is the general function of this domain. Some proteins known to contain a BED domain include animal, plant and fungi AC1 and Hobo-like transposases; "Caenorhabditis elegans" Dpy-20 protein, a predicted cuticular gene transcriptional regulator; Drosophila BEAF (boundary element-associated factor), thought to be involved in chromatin insulation; Drosophila DREF, a transcriptional regulator for S-phase genes; and tobacco 3AF1 and tomato E4/E8-BP1, light- and ethylene-regulated DNA binding proteins that contain two BED fingers. Most genes in this family are believed to have evolved from the hAT family of DNA transposons.


Glycoside hydrolase family 43

In molecular biology, glycoside hydrolase family 43 is a family of glycoside hydrolases.
Glycoside hydrolases are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycoside hydrolases, based on sequence similarity, has led to the definition of >100 different families. This classification is available on the CAZy web site, and also discussed at CAZypedia, an online encyclopedia of carbohydrate active enzymes.
Glycoside hydrolase family 43 CAZY GH_43 includes enzymes with the following activities, beta-xylosidase (), alpha-L-arabinofuranosidase (); arabinanase (), and xylanase (). The structure of arabinanase Arb43A from "Cellvibrio japonicus" reveals a five-bladed beta-propeller fold. A long V-shaped groove, partially enclosed at one end, forms a single extended substrate-binding surface across the face of the propeller.


D-stereospecific aminopeptidase

In molecular biology, D-stereospecific aminopeptidase (D-aminopeptidase) is an enzyme which catalyses the release of an N-terminal D-amino acid from a peptide, Xaa-|-Yaa-, in which Xaa is preferably D-Ala, D-Ser or D-Thr. D-amino acid amides and methyl esters also are hydrolyzed, as is glycine amide.
It is a dimeric enzyme with each monomer being composed of three domains. Domain B is organised to form a beta barrel made up of eight antiparallel beta strands. It is connected to domain A, the catalytic domain, by an eight-residue sequence, and also interacts with both domains A and C via non-covalent bonds. Domain B probably functions in maintaining domain C in a good position to interact with the catalytic domain. Domain C is organised to form a beta barrel made up of eight antiparallel beta strands. It is connected to domain B by a short linker sequence, and interacts extensively with the domain A, the catalytic domain. The gamma loop of domain C forms part of the wall of the catalytic pocket; domain C is in fact thought to confer substrate and inhibitor specificity to the enzyme.


Acyl-(acyl-carrier-protein) desaturase

In enzymology, an acyl-[acyl-carrier-protein] desaturase () is an enzyme that catalyzes the chemical reaction
The systematic name of this enzyme class is acyl-[acyl-carrier-protein], hydrogen-donor:oxygen oxidoreductase. Other names in common use include stearyl acyl carrier protein desaturase, and stearyl-ACP desaturase. This enzyme participates in polyunsaturated fatty acid biosynthesis. It employs one cofactor, ferredoxin.
Reaction.
The 3 substrates of this enzyme are stearoyl-(acyl-carrier-protein), reduced acceptor, and O2, whereas its 3 products are oleoyl-(acyl-carrier-protein), acceptor, and H2O.
The precise mechanism of this class of enzymes is not known, however recent studies using the kinetic isotope effect suggest that the rate limiting step is the removal of a hydrogen from the carbon nearest the carboxylic acid group. The diiron cluster moves through to a peroxo intermediate which can then dehydrate the short-lived alcohol intermediate, liberating water. There are a variety of specific enzymes within this class that attack using this mechanism, but do so at different points along the carbon chain of their respective fatty acids
Biological Function.
This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with oxidation of a pair of donors resulting in the formation of H2O.
This family of enzymes is found only in the plastids of higher plant cells, unlike other desaturases such as acyl-lipid desaturases and acyl-CoA desaturases. The regiospecific role of stearoyl-ACP desaturase is to initialise multiple desaturations by acyl-lipid desaturases. Oleic acid is formed from this reaction is transported to either the thylakoid or cytoplasm to complete desaturation.
Structural studies.
As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes , , , , and . and show the dramatic change in conformation of the enzyme when bound (2XZ1) and unbound (2XZ0). As a dimer, the fatty acid chain binds to a hydrophobic pocket at the interface of the two dimers. This central channel is mirrored by binding sites for the electron donors on either side.
The stabilisation of the diiron-oxo element required to catalyse the reaction has been of particular interest. Crystallographic studies suggest that the iron groups are held in place by the desaturase using aspartate and glutamate. A structure of aspartate-X-X-histidine was found to be a common motif in several plant species. This desaturase family can be further divided by the consensus motif used to hold the iron clusters in place. Of particular note are the "soluble" desaturases, which use carboxylic acid groups, whereas it is possible for some variants to use histidines instead. The histidine rich desaturases tend to be integral membrane proteins.
Structural studies strongly suggest that the animal form of this enzyme (Stearoyl-acyl-carrier-protein desaturase) is evolutionarily divergent from the forms found in plants and fungi. This is to be expected as the roles of the enzymes are different in both. For example, in insects, the desaturase is critical in the formation of ceramide, and for complex signalling molecules (pheremones), while in fungi, the function of the enzyme, and concentration of unsaturated lipids is regulated in response to function of growth temperature by controlling membrane fluidity in cells.
Potential Industrial Relevance.
This enzyme class plays a critical role in the biosynthesis of unsaturated fatty acids in plants, and are very specific to their substrates. A common theme in recent research has been to identify uncommon desaturases in various plants and isolate their genetic code. In particular, this can then be inserted into model cells (such as "Escherichia coli") and up-regulated through metabolic engineering to skew the composition of oils produced by the model cells.
This becomes a particularly lucrative endeavour if it becomes possible to successfully synthesise so-called Omega-3 fatty acids or other nutraceutical products from basic saturated fatty acids, and extract them from their hosts.


3beta-hydroxy-5beta-steroid dehydrogenase

In enzymology, a 3beta-hydroxy-5beta-steroid dehydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 3beta-hydroxy-5beta-pregnane-20-one and NADP+, whereas its 3 products are 5beta-pregnan-3,20-dione, NADPH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 3beta-hydroxy-5beta-steroid:NADP+ 3-oxidoreductase. Other names in common use include 3beta-hydroxysteroid 5beta-oxidoreductase, and 3beta-hydroxysteroid 5beta-progesterone oxidoreductase.


Ebola viral protein 24

Ebola viral protein 24 (eVP24) is considered a multifunctional secondary matrix protein present in viral particles. The broad roles eVP24 performs involve the formation of fully functional and infectious viral particles, promotion of filamentous nucleocapsid formation, mediation of host responses to infection, and suppression of the host innate immune system. It has been noted that eVP24 function can overlap with that of two other viral proteins; eVP40 matrix protein which functions in virus budding, and eVP35 which is also associated with immune suppression.
History.
Research.
The first recorded human outbreak of Ebola virus disease was in 1976 and since then, there has been considerable effort to define the progression of the disease and the virus responsible. The history of Ebola virus characterization is rather short as most research on the mechanisms employed by the virus have occurred in the last two decades. This is due to the intensive biohazard containment required for laboratory studies of the virus and the difficulty in obtaining samples for study, particularly in common outbreak regions. The isolation of viral cDNAs has allowed research into viral gene products to progress. The genome of the Ebola virus was found to encode seven proteins: glycoprotein; nucleoprotein; matrix proteins, VP40 and VP24; nonstructural proteins, VP30 and VP35; and viral polymerase. The functions of the viral proteins remained the last to be well investigated. In particular, eVP24 remained the least studied for some time.
Characterization.
eVP24 was initially described as a matrix protein that had similar properties and functions of eVP40. eVP24 was found to have characteristics of typical viral matrix proteins, such as a strong association with lipid bilayers and the ability to oligomerize to form tetramers. Like eVP40, eVP24 was found to be essential in virion assembly and budding. Later research indicated that the expression of eVP24 was required to switch from viral transcription and replication to virion assembly. A new role for eVP24 was found when its expression was monitored in rodent species where changes in eVP24 seemed to be responsible for enhancing virulence, indicating that adaption of Ebola in animal models occurs through mutations in eVP24. Additionally, eVP24 inhibits interferon signaling by competitively binding to karyopherins which blocks phosphorylated STAT1 nuclear import. In 2014, it was found that this mechanism interferes with the cells response to viral infection, which suppressed the innate immune response, allowing the virus to proliferate in the body.
Function.
eVP24 disrupts the signaling pathway of STAT1. The STAT1 protein is phosphorylated by interferons in response to viral infection causing it to express a non-classical nuclear localization signal and bind to the importin protein karyopherin-α (KPNA). Once bound to KPNA, STAT1 is transported to the nucleus where it stimulates gene transcription in response to viral infection.
Classical nuclear localization signals are bound by arms 2-4 or by 6-8 of KPNA while non-classical nuclear localization signals are bound by KPNA 1, 5 and 6 in arms 8-10 allowing non classical signals to be transported at the same time as classical signals, providing faster signaling of certain signals.
The eVP24 protein operates by binding to KPNA preventing the binding of STAT1. As a result, STAT1 is not able to elicit an immune response, however nuclear import is able to proceed as normal which may be important for viral replication. This means that eVP24 prevents the activation of an immune response against the Ebola virus without sacrificing its ability to have viral components transported to the nucleus or the target cell.
eVP24 provides Ebola with an advantages over other viruses which disrupt STAT1 because unlike most other viruses, eVP24 uses mimicry of the STAT1 protein. This makes it very unlikely for the host to develop an adaptation as mutations in KPNA which prevent eVP24 binding are also likely to prevent STAT1 signalling.
Mechanism.
eVP24 prevents the function of KPNA by binding in a region which overlaps with the binding region of STAT1. This is accomplished by the high binding affinity between KNPA and eVP24.
These proteins have very high complementarity in the binding interface, similar to the complementarity shown between antibodies and antigens. In addition, the binding interface is large; over 2000 angstroms squared of solvent accessible surface is buried by the binding. Overall binding takes place with very little conformational change in either protein.
There are three clusters of residues on eVP24 which form contacts to KPNA. These are located at residue positions 115 to 140, 184 to 186, and 201 to 207. Mutation of any single residue does not significantly reduce the binding of eVP24 to KPNA which demonstrates the robust mechanism of the viral protein.
KPNA proteins have 10 armadillo repeats each consisting of three alpha helices which determine their binding specificity, the second helix from ARM 9 and 10 form a hydrophobic core with helix 6 of eVP24 adding to the stability of the complex.
The binding sites for eVP24 and STAT1 have been shown to overlap. Mutation in any one of four residues in KPNA at positions 434, 474, 477 or 484 prevent binding to STAT1. Similarly, the mutations in residues 474, 477 or 484 of KPNA reduce the binding of eVP24. Additionally and critically, the binding of eVP24 does not prevent the binding of cargo proteins with classical nuclear localization signals as, like STAT1, eVP24 causes very little conformational changes in KPNA.
Effects on symptom progression.
eVP24 acts as an antagonist to PY-STAT1 on KPNA. With eVP24 being transported to the nucleus instead of STAT1, the interferon-stimulated genes IFN-α/IFN-β and IFN-γ are disrupted and the cell does not enter an antiviral state.
STAT1 has been shown to regulate the expression of certain immunoglobulins. More specifically, class switching from the predominant IgM to IgG2a was not present in STAT1-deficient cells. IgG2a plays a critical role in protection against pathogens and therefore without it, the cell is more susceptible to said pathogen.
STAT1 has also been shown to regulate cell death by the inhibition of anti-apoptotic proteins Bcl-2 and Bcl-xL. STAT1 also induces the expression of procaspases, which are important factors in apoptosis signaling. When nuclear transport of STAT1 is inhibited pro-apoptotic signalling is disrupted, leading to decreased cell death.
Current and future research.
The evasion of the host cell immune system is key in to the rapid replication and dispersion through the body by the Ebola virus. Current research is exploring how eVP24 enables this phenomenon to occur. The discovery of STAT1 nuclear import disruption by eVP24 binding to KPNA has already provided scientists with one mechanism for the inhibition of the immune response in the cell. Other current Ebola research is focused on developing treatments or vaccines against the virus. Early investigations into potential vaccines showed that in mice models, the highest levels of protection occurred after vaccination with viral-like particles expressing eVP24. However, at that time the role of eVP24 was still largely unknown. In the wake of the 2014 Ebola outbreak in West Africa, the largest and deadliest outbreak to date, there has been a considerable increase in research focused on developing a vaccine for Ebola.


Epicatechin


3-ethylmalate synthase

In enzymology, a 3-ethylmalate synthase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are butanoyl-CoA, H2O, and glyoxylate, whereas its two products are 3-ethylmalate and CoA.
This enzyme belongs to the family of transferases, specifically those acyltransferases that convert acyl groups into alkyl groups on transfer. The systematic name of this enzyme class is butanoyl-CoA:glyoxylate C-butanoyltransferase (thioester-hydrolysing, 1-carboxypropyl-forming). Other names in common use include 2-ethyl-3-hydroxybutanedioate synthase, and 3-ethylmalate glyoxylate-lyase (CoA-butanoylating). This enzyme participates in glyoxylate and dicarboxylate metabolism.


5-phytase

In enzymology, a 5-phytase () is an enzyme that catalyzes the chemical reaction
"myo"-Inositol hexakisphosphate is also known as phytic acid.
These enzymes belongs to the family of hydrolases, specifically those acting on phosphoric monoester bonds. The systematic name of this enzyme class is "myo"-inositol-hexakisphosphate 5-phosphohydrolase.
Prevalence.
Of the hundreds of phytase enzymes that have been characterized in the literature, only two have been characterized as 5-phytases. A histidine acid phosphatases purified from lily pollen and a protein tyrosine phosphatase-like phytase from "Selenomonas ruminantium" subsp. "lactilytica" were both found to have specificity for the 5-phosphate position of "myo"-inositol hexakisphosphate.
Structural studies.
As of late 2007, only the phytase purified from lily pollen had its structure solved, with PDB accession codes , , , , , and .


2-deoxyglucose-6-phosphatase

In enzymology, a 2-deoxyglucose-6-phosphatase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 2-deoxy-D-glucose 6-phosphate and H2O, whereas its two products are 2-deoxy-D-glucose and phosphate.
This enzyme belongs to the family of hydrolases, specifically those acting on phosphoric monoester bonds. The systematic name of this enzyme class is 2-deoxy-D-glucose-6-phosphate phosphohydrolase. This enzyme is also called 2-deoxyglucose-6-phosphate phosphatase.


Acyl-CoA-binding protein

In molecular biology, the Acyl-CoA-binding protein (ACBP) is a small (10 Kd) protein that binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. ACBP is also known as diazepam binding inhibitor (DBI) or endozepine (EP) because of its ability to displace diazepam from the benzodiazepine (BZD) recognition site located on the GABA type A receptor. It is therefore possible that this protein also acts as a neuropeptide to modulate the action of the GABA receptor.
ACBP is a highly conserved protein of about 90 amino acids that is found in all four eukaryotic kingdoms, Animalia, Plantae, Fungi and Protista, and in some eubacterial species.
Although ACBP occurs as a completely independent protein, intact ACB domains have been identified in a number of large, multifunctional proteins in a variety of eukaryotic species. These include large membrane-associated proteins with N-terminal ACB domains, multifunctional enzymes with both ACB and peroxisomal enoyl-CoA Delta(3), Delta(2)-enoyl-CoA isomerase domains, and proteins with both an ACB domain and ankyrin repeats.
The ACB domain consists of four alpha-helices arranged in a bowl shape with a highly exposed acyl-CoA-binding site. The ligand is bound through specific interactions with residues on the protein, most notably several conserved positive charges that interact with the phosphate group on the adenosine-3'phosphate moiety, and the acyl chain is sandwiched between the hydrophobic surfaces of CoA and the protein.
Other proteins containing an ACB domain include:


LysC

LysC is a prokaryotic aspartokinase involved in the biosynthesis of the amino acid lysine. It is found in a variety of bacteria, including "Bacillus subtilis", "Escherichia coli" and "Corynebacterium glutamicum". It is notable for containing a riboswitch, a structure in its messenger RNA that prevents its translation when bound to lysine. Such lysine riboswitch thus acts as a mechanism of negative feedback.


SRPX

Sushi repeat-containing protein SRPX is a protein that in humans is encoded by the "SRPX" gene. Bioinformatics analysis suggests the SRPX protein is a peroxiredoxin.


Lipomatosis

Lipomatosis is believed to be an autosomal dominant condition in which multiple lipomas are present on the body. Many discrete, encapsulated lipomas form on the trunk and extremities, with relatively few on the head and shoulders. In 1993, a genetic polymorphism within lipomas was localized to chromosome 12q15, where the HMGIC gene encodes the high-mobility-group protein isoform I-C. This is one of the most commonly found mutations in solitary lipomatous tumors but lipomas often have multiple mutations. Reciprocal translocations involving chromosomes 12q13 and 12q14 have also been observed within.
Although this condition is benign, it can sometimes be very painful depending on location of the lipomas. Some patients who are concerned with cosmetics seek removal of individual lipomas. Removal can include simple excision, endoscopic removal, or liposuction.
Other entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, benign symmetric lipomatosis (Madelung disease), Dercum's Disease, familial lipodystrophy, hibernomas, epidural steroid injections with epidural lipomatosis, and familial angiolipomatosis.


KacL

KacL may refer to:


Ethyl protocatechuate

Ethyl protocatechuate is a phenolic compound. It can be found in the peanut seed testa. It is also present in wine. It is the ethylic ester of protocatechuic acid.
The compound is a prolyl 4-hydroxylase inhibitor and can be used to protect the myocardium.


Nepicastat

Nepicastat (INN, codenamed SYN117, RS-25560-197) is an inhibitor of dopamine beta-hydroxylase, an enzyme that catalyzes the conversion of dopamine to norepinephrine.
It has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated as such. As of 2012, clinical trials to assess nepicastat as a treatment for post-traumatic stress disorder (PTSD) and cocaine dependence have been completed. In Phase 2 study treatment with nepicastat was not effective in relieving PTSD-associated symptoms when compared to placebo. The study was funded by the U.S. Department of Defense.


Dafachronic acid

Dafachronic acids are steroid hormones activate the nuclear receptor Daf-12/NR1J1 in "Caenorhabditis elegans" and related organisms, include Δ4-dafachronic acid and Δ7-dafachronic acid. Both are generated by Daf-9/CYP22A1 from respective precursors.


Ammonia transporter

Ammonia transporters (TC# 1.A.11) are structurally related membrane transport proteins called Amt proteins (ammonia transporters) in bacteria and plants, methylammonium/ammonium permeases (MEPs) in yeast, or Rhesus (Rh) proteins in chordates. In humans, the RhAG, RhBG, and RhCG Rhesus proteins constitute solute carrier family 42 whilst RhD and RhCE form the Rh blood group system. The three-dimensional structure of the ammonia transport protein AmtB from "Escherichia coli" has been determined by x-ray crystallography revealing a hydrophobic ammonia channel. The human RhCG ammonia transporter was found to have a similar ammonia-conducting channel structure. It was proposed that the erythrocyte Rh complex is a heterotrimer of RhAG, RhD, and RhCE subunits in which RhD and RhCE might play roles in anchoring the ammonia-conducting RhAG subunit to the cytoskeleton. Based on reconstitution experiments, purified RhCG subunits alone can function to transport ammonia. RhCG is required for normal acid excretion by the mouse kidney and epididymis.
Structure.
The structure of the ammonia channel from "E. coli", was, at the time of its publication, the highest resolution structure of any integral membrane protein. It shows a trimer of subunits, each made up of 11 transmembrane segments (TMSs) and containing a pseudo two-fold symmetry. Each monomer contains a hydrophobic ammonia conducting channel.
While prokaryotic ammonia channel proteins have an N-terminal region which acts as a signal sequence and is cleaved in the mature protein, the Rhesus glycoproteins retain this as a 12th transmembrane helix in the mature protein.
Substrate specificity.
Most functionally characterized members of the family are ammonium uptake transporters. Some, but not other Amt proteins also transport methylammonium. Detailed phylogenetic analyses of plant homologues have been published. In "E. coli", NH4+, rather than NH3, may be the substrate of AmtB, but controversy still exists. If NH4+ is transported, K+ possibly serves as a counter ion in an antiport process with K+, and that one histidine removes a proton off of NH4+ to yield NH3.
Transport reaction.
The generalized transport reaction catalyzed by members of the Amt family are suggested to be:
Mechanism.
The X-ray structures have revealed that the pore of the Amt and Rh proteins is characterized by a hydrophobic portion about 12 Å long, in which electronic density was observed in the crystallographic study of AmtB from "Escherichia coli". This electronic density was initially only observed when crystals were grown in the presence of ammonium, and was thus attributed to ammonia molecules. The Amt/Rh protein mechanism might involve the single-file diffusion of NH3 molecules. However, the pore could also be filled with water molecules. The possible presence of water molecules in the pore lumen calls for a reassessment of the notion that Amt/Rh proteins work as plain NH3 channels. Indeed, functional experiments on plant ammonium transporters and Rh proteins suggest a variety of permeation mechanisms including the passive diffusion of NH3, the antiport of NH4+/H+, the transport of NH4+, or the cotransport of NH3/H+. Lamoureux "et al." discuss these mechanisms in light of functional and simulation studies on the AmtB transporter.
Regulation.
In "E. coli" the AmtB gene is expressed only under limiting nitrogen levels to yield the AmtB protein. It is co-expressed with the GlnK gene which encodes a PII protein. This protein is also trimeric and remains in the cytoplasm. It is covalently modified by a U/U deuridylylated group at Y51. The hydrolyzed product, adenosine 5'-diphosphate, orients the surface of GlnK for AmtB blockade. When nitrogen levels outside the cell rise, the ammonia channel must be deactivated to prevent excessive ammonia entering the cell (where ammonia would be combined with glutamate to make glutamine, utilizing ATP and thereby depleting the cell's ATP reserves). This deactivation is achieved by deuridylylation of the GlnK protein which then binds to the cytoplasmic face of AmtB and inserts a loop into the ammonia conducting pore. At the tip of this loop is an arginine residue which sterically blocks the channel.
Human ammonia transporter-related proteins.
RHAG, RHBG, RHCE, RHCG RHD


UQCC3

Ubiquinol-cytochrome c reductase complex assembly factor 3 is a protein that in humans is encoded by the "UQCC3" gene. Located in mitochondria, this protein is involved in the assembly of mitochondrial Complex III, stabilizing supercomplexes containing Complex III. Mutations in the "UQCC3" gene cause Complex III deficiency with symptoms of hypoglycemia, hypotonia, lactic acidosis, and developmental delays. This protein plays an important role as an antiviral factor, bolstering the ability of cells to inhibit viral replication, independent of interferon production. The UQCC3 protein can be cleaved by OMA1 metalloprotease during mitochondrial depolarization, targeting the cell for apoptosis. Depletion of this protein alters cardiolipin composition, causing cellular and mitochondrial defects.
Structure.
The "UQCC3" gene is located on the q arm of chromosome 11 in position 12.3 and spans 2,036 base pairs. The gene produces a 10.1 kDa protein composed of 93 amino acids. This protein faces the intermembrane space. It possesses an N-terminal signal peptide and a signal transmembrane structure, in addition to several phosphorylation sites. The secondary structure of this protein is made up mostly of random coils and alpha helices. Alpha helices 2 and 3 bind to cardiolipin.
Function.
The "UQCC3" gene encodes a protein that functions in complex III assembly, downstream of assembly factors UQCC1 and UQCC2. This is evidenced by the observation that UQCC3 levels are reduced in cells with decreased levels of UQCC1 and UQCC2, but lack of the UQCC3 protein does not affect levels of UQCC1 and UQCC2. Predicted to be a secretary protein with small molecular weight, this protein has important functions in cellular proliferation and antiviral innate immune regulation. Expression of this protein is ubiquitous in carcinomas, along with normal tissues. During the early stages of Complex III assembly, the UQCC3 protein stabilizes supercomplexes containing Complex III, most notably the III2/IV supercomplex.
Clinical Significance.
In the sole recorded case of a mutation in the "UQCC3" gene, a patient with a homozygous missense mutation presented with nuclear type 9 complex III deficiency, displaying symptoms of hypoglycemia, hypotonia, lactic acidosis, severe delayed psychomotor development, and other developmental delay. The patient also had decreased levels of cytochrome b within Complex III.
The UQCC3 protein also has a role as an antiviral factor, independent of interferon production. Levels of this protein increase in response to a viral infection, improving the ability of cells to inhibit viral replication. Overexpression of the "UQCC3" gene increases transcription of OAS3 while knockdown of RNase L or OAS3 hampers the antiviral effect of UQCC3. Signaling from UQCC3 to the OAS-RNase L system is independent of interferon production. This protein is also regulated by expression of the double-stranded RNA-dependent protein kinase EIF2AK2.
Depleted levels of the UQCC3 protein cause impaired respiration and subtle yet significant alterations in cardiolipin composition, which then result in abnormal crista morphology, increased sensitivity to apoptosis, and decreased levels of ATP. Furthermore, mitochondrial depolarization causes OMA1 metalloprotease to cleave the UQCC3 protein; effectively, this mechanism targets cells with damaged mitochondria for apoptosis.
Interactions.
This protein associates with the rest of mitochondrial Complex III and has protein-protein interactions with PHLDA3.


Polythiazide

Polythiazide is a thiazide diuretic. A diuretic is any substance that promotes the production of urine.


Bacillus haemolytic enterotoxin

In molecular biology, the Bacillus haemolytic enterotoxin family of proteins consists of several Bacillus haemolytic enterotoxins (HblC, HblD, HblA, NheA, and NheB), which can cause food poisoning in humans. Haemolysin BL (encoded by HBL) and non-haemolytic enterotoxin (encoded by NHE), represent the major enterotoxins produced by "Bacillus cereus". Most of the cytotoxic activity of "B. cereus" isolates has been attributed to the level of Nhe, which may indicate a highly diarrheic potential. The exact mechanism by which B. cereus causes diarrhoea is unknown. Hbl, cytotoxin K (CytK) and Nhe are all putative causes.
Both Hbl and Nhe are three-component cytotoxins composed of a binding component, B, and two lytic components, L1 and L2. All three subunits act synergically to cause hemolysis. Maximal cytotoxicity of Nhe against epithelia is dependent on all three components. Nhe has haemolytic activity against erythrocytes from a variety of species. It is possible that the common structural and functional properties of these toxins indicate that the Hbl/Nhe and ClyA families of toxins constitute a superfamily of pore-forming cytotoxins. Haemolysin BL and non-haemolytic enterotoxin production are both influenced by pH and micro.


KDM5A

Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the "KDM5A" gene.
Function.
The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein which regulates cell proliferation. It was formerly known as Retinoblastoma Binding Protein 2 (RBP2). This protein also interacts with rhombotin-2 which functions distinctly in erythropoiesis and in T-cell leukemogenesis. Rhombotin-2 is thought to either directly affect the activity of the encoded protein or may indirectly modulate the functions of the retinoblastoma protein by binding to this protein. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
The "Drosophila" homolog, LID, was found to be an H3K4 histone demethylase that binds to c-Myc. It was recently renamed to Lysine Demethylase 5A (KDM5A).
Enzymatically can be designated as a trimethyllysine dioxygenase, which is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily ().
Interactions.
JARID1A has been shown to interact with Estrogen receptor alpha, LMO2 and Retinoblastoma protein.
JARID1A is a major component of the circadian clock, the upregulation of which at the end of the sleep phase blocks HDAC1 activity. Blocking HDAC1 activity results in an upregulation of CLOCK and BMAL1 and consequent upregulation of PER proteins. The PSF (polypyrimidine tract-binding protein-associated splicing factor) within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription.
Knockdown of JARID1A promoted osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo and resulted in marked increases of mRNA expression of osteogenesis-associated genes such as alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX). RBP2 was shown to occupy the promoters of OSX and OC to maintain the level of the H3K4me3 mark by chromatin immunoprecipitation assays. RBP2 was also physically and functionally associated with RUNX2, an essential transcription factor that governed osteoblastic differentiation. RUNX2 knockdown impaired the repressive activity of RBP2 in osteogenic differentiation of human adipose-derived stromal cells.


Hydroxyandrostenedione

Hydroxyandrostenedione may refer to:


Endopeptidase La

Endopeptidase La (, "ATP-dependent serine proteinase", "lon proteinase", "protease La", "proteinase La", "ATP-dependent lon proteinase", "ATP-dependent protease La", "Escherichia coli proteinase La", "Escherichia coli serine proteinase La", "gene lon protease", "gene lon proteins", "PIM1 protease", "PIM1 proteinase", "serine protease La") is an enzyme. This enzyme catalyses the following chemical reaction
This enzyme is a product of the lon gene in "Escherichia coli".


Diacetyl reductase

Diacetyl reductase is the name of two acetoin forming enzymes:


Nicotinamide adenine dinucleotide (phosphate) transhydrogenase

Nicotinamide adenine dinucleotide (phosphate) transhydrogenase may stand for


Cadherin

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that are important in the formation of adherens junctions to bind cells with each other. Cadherins are a class of type-1 transmembrane proteins, and they are dependent on calcium (Ca2+) ions to function, hence their name. Cell-cell adhesion is mediated by extracellular cadherin domains, whereas the intracellular cytoplasmic tail associates with numerous adaptors and signaling proteins, collectively referred as the cadherin adhesome.
The cadherin family is essential in maintaining the cell to cell contact between each other and regulating for cytoskeletal complexes. The cadherin superfamily includes cadherins, protocadherins, desmogleins, desmocollins, and more. In structure, they share "cadherin repeats", which are the extracellular Ca2+-binding domains. There are multiple classes of cadherin molecules, each designated with a prefix (in general, noting the types of tissue with which it is associated). Classical cadherins maintain the tone of tissues by forming a homodimer while desmosomes are the heterodimers. The intracellular portion of classical cadherins has regulatory proteins that helps the cadherins joining the actin cytoskeleton. Although classical cadherins take a role in cell layer formation and structure formation, desmosomal cadherins focus on resisting the catastrophe towards the cells. Desmosomal cadherins are responsible to maintain the function of desmosomes that is to overturn the mechanical stress of the tissues. Similar to classical cadherins, desmosomal cadherins has a single transmembrane domain, five EC repeats, and an intracellular domain. Two types of desmosomal cadherins exist, and they are called desmogleins and desmocollins that contains an intracellular anchor and cadherin like sequence (ICS). The adaptor proteins that associate with desmosomal cadherins are plakoglobin (related to formula_1-catenin), plakophilins (p120 catenin subfamily), and desmoplakins. The major function of desmoplakins to bind to intermediate filament thorough interaction with plakoglobin that attaches to ICS of desmogleins and desmocollins and plakophilins. Atypical cadherins are different from other types of cadherins and consist of one or more extracellular repeat domains. The components that build an atypical cadherin are flamingo (seven pass transmembrane) and Dcad102F-like cadherins. Their job is to take part in signaling pathway instead of performing cell-cell adhesion.
It has been observed that cells containing a specific cadherin subtype tend to cluster together to the exclusion of other types, both in cell culture and during development. For example, cells containing N-cadherin tend to cluster with other N-cadherin-expressing cells. However, it has been noted that the mixing speed in the cell culture experiments can have an effect on the extent of homotypic specificity. In addition, several groups have observed heterotypic binding affinity (i.e., binding of different types of cadherin together) in various assays. One current model proposes that cells distinguish cadherin subtypes based on kinetic specificity rather than thermodynamic specificity, as different types of cadherin homotypic bonds have different lifetimes.
Structure.
Cadherins are synthesized as polypeptides and undergo many post-translational modifications to become the proteins which mediate cell-cell adhesion and recognition. These polypeptides are approximately 720–750 amino acids long. Each cadherin has a small C-terminal cytoplasmic component, a transmembrane component, and the remaining bulk of the protein is extra-cellular (outside the cell). The transmembrane component consists of single chain glycoprotein repeats.  Because cadherins are Ca2+ dependent, they have five tandem extracellular domain repeats that act as the binding site for Ca2+ ions.  Their extracellular domain interacts with two separate "trans" dimer conformations: strand-swap dimers (S-dimers) and X-dimers. To date, over 100 types of cadherins in humans have been identified and sequenced.
 The functionality of cadherins relies upon the formation of two identical subunits, known as homodimers. The homodimeric cadherins create cell-cell adhesion with cadherins present in the membranes of other cells through changing conformation from "cis"-dimers to "trans"-dimers. Once the cell-cell adhesion between cadherins present in the cell membranes of two different cells has formed, adherens junctions can then be made when protein complexes, usually composed of α-, β-, and γ-catenins, bind to the cytoplasmic portion of the cadherin. Regulatory proteins include p-120 catenin, formula_2-catenin,  formula_1-catenin, and vinculin. Binding of p-120 catenin and formula_1-catenin to the homodimer increases the stability of the classical cadherin. formula_2-catenin is engaged by p120-catenin complex, where vinculin is recruited to take a role in indirect association with actin cytoskeleton. However, cadherin-catenin complex can also bind directly to the actin without the help of vinculin. Moreover, the strength of cadherin adhesion can increase by dephosphorylation of p120 catenin and the binding of formula_2-catenin and vinculin.
Function.
Development.
Cadherins behave as both receptors and ligands for other molecules. During development, their behavior assists as properly positioning cells: they are responsible for the separation of the different tissue layers and for cellular migration. In the very early stages of development, E-cadherins (epithelial cadherin) are most greatly expressed. Many cadherins are specified for specific functions in the cell, and they are differentially expressed in a developing embryo. For example, during neurulation, when a neural plate forms in an embryo, the tissues residing near the cranial neural folds have decreased N-cadherin expression. Conversely, the expression of the N-cadherins remains unchanged in other regions of the neural tube that is located on the anterior-posterior axis of the vertebrate. N-cadherins have different functions that maintain the cell structure, cell-cell adhesion, internal adhesions. They participate greatly in keeping the ability of the structured heart due to pumping and release blood. Because of the contribution of N-cadherins adhering strongly between the cardiomyocytes, the heart can overcome the fracture, deformation, and fatigue that can result from the blood pressure. N-cadherin takes part in the development of the heart during embryo, especially in sorting out of the precardiac mesoderm. N-cadherins are robustly expressed in precardiac mesoderm, but they do not take a role in cardiac linage. An embryo with N-cadherin mutation still forms the primitive heart tube; however, N-cadherin deficient mice will have difficulties in maintaining the cardiomyocytes development. The myocytes of these mice will end up with dissociated myocytes surrounding the endocardial cell layer when they cannot preserve the cell adhesion due to the heart starting to pump. As a result, the cardiac outflow tract will be blocked causing cardiac swelling.The expression of different types of cadherins in the cells varies dependent upon the specific differentiation and specification of an organism during development. Cadherins play a vital role in the migration of cells through the epithelial-mesenchymal transition (EMT), which requires cadherins to form adherents junctions with neighboring cells. In neural crest cells, which are transient cells that arise in the developing organism during gastrulation and function in the patterning of the vertebrate body plan, the cadherins are necessary to allow migration of cells to form tissues or organs. In addition, cadherins that are responsible in the EMT event in early development have also been shown to be critical in the reprogramming of specified adult cells into a pluripotent state, forming induced pluripotent stem cells (iPSCs).
After development, cadherins play a role in maintaining cell and tissue structure, and in cellular movement. Regulation of cadherin expression can occur through promoter methylation among other epigenetic mechanisms.
Tumour metastasis.
The E-cadherin–catenin complex plays a key role in cellular adhesion; loss of this function has been associated with increased invasiveness and metastasis of tumors. The suppression of E-cadherin expression is regarded as one of the main molecular events responsible for dysfunction in cell-cell adhesion, which can lead to local invasion and ultimately tumor development. Because E-cadherins play an important role in tumor suppression, they are also referred to as the "suppressors of invasion".
Correlation to cancer.
It has been discovered that cadherins and other additional factors are correlated to the formation and growth of some cancers and how a tumor continues to grow. The E-cadherins, known as the epithelial cadherins, are on the surface of one cell and can bind with those of the same kind on another to form bridges. The loss of the cell adhesion molecules, E cadherins, is causally involved in the formation of epithelial types of cancers such as carcinomas. The changes in any types of cadherin expression may not only control tumor cell adhesion but also may affect signal transduction leading to the cancer cells growing uncontrollably.
In epithelial cell cancers, disrupted cell to cell adhesion might lead to the development of secondary malignant growths; they are distant from the primary site of cancer and can result from the abnormalities in the expression of E-cadherins or its associated catenins. CAMs such as the cadherin glycoproteins that normally function as the glue and holds cells together act as important mediators of cell to cell interactions. E-cadherins, on the surface of all epithelial cells, are linked to the actin cytoskeleton through interactions with catenins in the cytoplasm. Thus, anchored to the cytoskeleton, E-cadherins on the surface of one cell can bind with those on another to form bridges. In epithelial cell cancers, disrupted cell-cell adhesion that might lead to metastases can result from abnormalities in the expression of E-cadherin or its associated catenins.
Correlation to endometrium and embryogenesis.
This family of glycoproteins is responsible for calcium-dependent mechanism of intracellular adhesion. E-cadherins are crucial in embryogenesis during several processes, including gastrulation, neurulation, and organogenesis. Furthermore, suppression of E-cadherins impairs intracellular adhesion. The levels of these molecules increase during the luteal phase while their expression is regulated by progesterone with endometrial calcitonin.
Types.
There are said to be over 100 different types of cadherins found in vertebrates, which can be classified into four groups: classical, desmosomal, protocadherins, and unconventional. These large amount of diversities are accomplished by having multiple cadherin encoding genes combined with alternative RNA splicing mechanisms. Invertebrates contain fewer than 20 types of cadherins.
Classical.
Different members of the cadherin family are found in different locations.
Protocadherins.
Protocadherins are the largest mammalian subgroup of the cadherin superfamily of homophilic cell-adhesion proteins.


Munch (candy bar)

Munch is a peanut bar manufactured by Mars, Incorporated and sold in the United States. The bar was introduced in 1970 as the Snickers Munch Peanut Brittle Bar and was later relabeled "Munch". It is made of only seven ingredients: peanuts, sugar, butter, corn syrup, palm oil, salt and soy lecithin.
The candy bar contains no chocolate and is comparable to peanut brittle, though the Munch bar has a higher density of peanuts compared to most brittles.
Due to its short list of simple ingredients, it is marketed as being healthy and natural.


Cis-dihydroethylcatechol dehydrogenase

In enzymology, a cis-dihydroethylcatechol dehydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are cis-1,2-dihydro-3-ethylcatechol and NAD+, whereas its 3 products are 3-ethylcatechol, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is cis-1,2-dihydro-3-ethylcatechol:NAD+ oxidoreductase. This enzyme participates in ethylbenzene degradation.


Bombinin

The bombinin family of antimicrobial peptides includes the bombinin and maximin proteins from "Bombina maxima" (Giant fire-bellied toad). Two groups of antimicrobial peptides have been isolated from skin secretions of "B. maxima". Peptides in the first group, named maximins 1, 2, 3, 4 and 5, are structurally related to bombinin-like peptides (BLPs). Unlike BLPs, sequence variations in maximins occurred all through the molecules. In addition to the potent antimicrobial activity, cytotoxicity against tumour cells and spermicidal action of maximins, maximin 3 possessed a significant anti-Simian-Human immunodeficiency virus (HIV) activity. Maximins 1 and 3 have been found to be toxic to mice. Peptides in the second group, termed maximins H1, H2, H3 and H4, are homologous with bombinin H peptides.


Dihydrocarveol dehydrogenase

Dihydrocarveol dehydrogenase (, "carveol dehydrogenase (ambiguous)") is an enzyme with systematic name "menth-8-en-2-ol:NAD+ oxidoreductase". This enzyme catalyses the following chemical reaction
This enzyme from the Gram-positive bacterium "Rhodococcus erythropolis" DCL14 forms part of the carveol and dihydrocarveol degradation pathway. The enzyme accepts all eight stereoisomers of menth-8-en-2-ol as substrate, although some isomers are converted faster than others. The preferred substrates are (+)-neoisodihydrocarveol, (+)-isodihydrocarveol, (+)-dihydrocarveol and (-)-isodihydrocarveol.


Tozasertib

Tozasertib (VX-680) is an aurora inhibitor.


Supersecondary structure

A supersecondary structure is a compact three-dimensional protein structure of several adjacent elements of a secondary structure that is smaller than a protein domain or a subunit. Supersecondary structures can act as nucleations in the process of protein folding.
Examples.
Helix supersecondary structures.
Helix hairpin.
A helix hairpin, also known as an alpha-alpha hairpin, is composed of two antiparallel alpha helices connected by a loop of two or more residues. True to its name, it resembles a hairpin. A longer loop has a greater number of possible conformations. If short strands connect the helices, then the individual helices will pack together through their hydrophobic residues. The function of a helix hairpin is unknown; however, a four helix bundle is composed of two helix hairpins, which have important ligand binding sites.
Helix corner.
A helix corner, also called an alpha-alpha corner, has two alpha helices almost at right angles to each other connected by a short 'loop'. This loop is formed from a hydrophobic residue. The function of a helix corner is unknown.
Helix-loop-helix.
The helix-loop-helix structure has two helices connected by a 'loop'. These are fairly common and usually bind ligands. For example, calcium binds with the carboxyl groups of the side chains within the loop region between the helices.
Helix-turn-helix.
The helix-turn-helix motif is important for DNA binding and is therefore in many DNA binding proteins.
Beta sheet supersecondary structures.
Beta hairpin.
A beta hairpin is a common supersecondary motif composed of two anti-parallel beta strands connected by a loop. The structure resembles a hairpin and is often found in globular proteins.
The loop between the beta strands can range anywhere from 2 to 16 residues. However, most loops contain less than seven residues. Residues in beta hairpins with loops of 2, 3, or 4 residues have distinct conformations. However, a wide range of conformations can be seen in longer loops, which are sometimes referred to as 'random coils'. A beta-meander consists of "consecutive" antiparallel-beta strands linked by hairpins.
Two residue loops are called beta turns or reverse turns. Type I' and Type II' reverse turns occur most frequently because they have less steric hindrance than Type I and Type II turns. The function of beta hairpins is unknown.
Beta corner.
A beta hairpin has two antiparallel beta strands that are at about a 90 degree angle to each other. It is formed by a beta hairpin changing direction with one strand having a glycine residue and the other strand having a beta bulge. Beta corners have no known function.
Greek key motif.
A Greek key motif has four features:
The Greek key motif has its name because the structure looks like the pattern seen on Greek urns. This motif has no known function.
Other.
β-sheets (composed of multiple hydrogen-bonded individual β-strands) are sometimes considered a secondary or supersecondary structure.
Mixed supersecondary structures.
Beta-alpha-beta motifs.
A beta-alpha-beta motif is composed of two beta strands joined by an alpha helix through connecting loops. The beta strands are parallel, and the helix is also almost parallel to the strands. This structure can be seen in almost all proteins with parallel strands. The loops connecting the beta strands and alpha helix can vary in length and often binds ligands.
Beta-alpha-beta helices can be either left-handed or right-handed. When viewed from the N-terminal side of the beta strandes, so that one strand is on top of the other, a left-handed beta-alpha-beta motif has the alpha helix on the left side of the beta strands. The more common right-handed motif would have an alpha helix on the right side of the plane containing the beta strands.
Rossman fold.
Rossman folds, named after Michael Rossman, consist of 3 beta strands and 2 helices in an alternating fashion: beta strand, helix, beta strand, helix, beta strand. This motif tends to reverse the direction of the chain within a protein. Rossman folds have an important biological function in binding nucleotides such as NAD within most dehydrogenases.


2,5-diaminovalerate transaminase

In enzymology, a 2,5-diaminovalerate transaminase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 2,5-diaminopentanoate and 2-oxoglutarate, whereas its two products are 5-amino-2-oxopentanoate and L-glutamate.
It employs one cofactor, pyridoxal phosphate.
Nomenclature.
This enzyme belongs to the family of transferases, specifically the transaminases, which transfer nitrogenous groups. The systematic name of this enzyme class is 2,5-diaminopentanoate:2-oxoglutarate aminotransferase. Other names in common use include diamino-acid transaminase, and diamino acid aminotransferase.


Ent-isokaurene synthase

Ent-isokaurene synthase (, "OsKSL5i", "OsKSL6") is an enzyme with systematic name "ent-copalyl-diphosphate diphosphate-lyase (cyclizing, ent-isokaurene-forming)". This enzyme catalyses the following chemical reaction
Two enzymes of the rice sub-species "Oryza sativa" ssp. indica, OsKSL5 and OsKSL6, produce ent-isokaurene.


Arfaptin

In molecular biology, the arfaptin domain is a protein domain which interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The structure of arfaptin shows that upon binding to a small GTPase, arfaptin forms an elongated, crescent-shaped dimer of three-helix coiled-coils. The N-terminal region of ICA69 is similar to arfaptin.


Trypsinogen

Trypsinogen () is the precursor form (or zymogen) of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by enteropeptidase, which is found in the intestinal mucosa. Once activated, the trypsin can cleave more trypsinogen into trypsin, a process called autoactivation. Trypsin cleaves the peptide bond on the carboxyl side of basic amino acids such as arginine and lysine.
Function.
Trypsinogen is the proenzyme precursor of trypsin. Trypsinogen (the inactive form) is stored in the pancreas so that it may be released when required for protein digestion. The pancreas stores the inactive form trypsinogen because the active trypsin would cause severe damage to the tissue of the pancreas. Trypsinogen is released by the pancreas into the second part of the duodenum, via the pancreatic duct, along with other digestive enzymes.
Activation of trypsinogen.
Trypsinogen is activated by enteropeptidase (also known as enterokinase). Enteropeptidase is produced by the mucosa of duodenum and it cleaves the peptide bond of trypsinogen after residue 15, which is a lysine. The N-terminal peptide is discarded, and a slight rearrangement of the folded protein occurs. The newly formed N-terminal residue (residue 16) inserts into a cleft, where its α-amino group forms an ion pair with the aspartate near the active site serine, and results in the conformational rearrangement of other residues. The amino group of Gly 193 orientates itself into the correct position, which completes the oxyanion hole in active site, thereby activating the protein. Since trypsin also cleaves the peptide bond after an arginine or a lysine, it can cleave other trypsinogen, and the activation process therefore becomes autocatalytic.
Safeguards against trypsinogen activation.
Trypsin is produced, stored and released as the inactive trypsinogen to ensure that the protein is only activated in the appropriate location. Premature trypsin activation can be destructive and may trigger a series of events that lead to pancreatic self-digestion. In normal pancreas, around 5% of trypsinogens are thought to get activated, therefore there are a number of defenses against such inappropriate activation. Trypsinogen is stored in intracellular vesicles in the pancreas called zymogen granules whose membranous walls are thought to be resistant to enzymatic degradation. A further safeguard against inappropriate trypsin activation is the presence of inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and serine protease inhibitor Kazal-type 1 (SPINK1), which binds to any trypsin formed. Trypsin autocatalytic activation of trypsinogen is also a slow process due to the presence of a large negative charge on the conserved N-terminal hexapeptide of trypsinogen, which repels the aspartate on the back of trypsin's specificity pocket. Trypsin may also inactivate other trypsin by cleavage.
Serum trypsinogen.
Serum trypsinogen is measured using a blood test. High levels are seen in acute pancreatitis and cystic fibrosis.
Trypsinogen isoforms.
Three isoforms of trypsinogens may be found in human pancreatic juice. These are the cationic, anionic, and meso trypsinogen, and they account for 23.1%, 16%, and 0.5% of total pancreatic secretory proteins, respectively. Other forms of trypsinogen have been found in other organisms.
Diseases.
The inappropriate activation of trypsinogen in the pancreas can lead to pancreatitis. Some type of pancreatitis may be associated with mutant forms of trypsinogen. A mutation at Arg 117, a trypsin-sensitive site, in cationic trypsinogen has been implicated in hereditary pancreatitis, a rare form of early-onset genetic disorder. Arg 117 may be a fail-safe mechanism by which trypsin, when activated within the pancreas, may become inactivated, and loss of this cleavage site would result in a loss of control and permit autodigestion resulting in pancreatitis. Other mutations have also been found that are linked to pancreatitis.


PAX3

The PAX3 (paired box gene 3) gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.
Transcript splicing.
Alternative splicing and processing generates multiple PAX3 isoforms that have been detected at the mRNA level. PAX3e is the longest isoform and consists of 10 exons that encode a 505 amino acid protein. In other mammalian species, including mouse, the longest mRNAs correspond to the human PAX3c and PAX3d isoforms, which consist of the first 8 or 9 exons of the PAX3 gene, respectively. Shorter PAX3 isoforms include mRNAs that skip exon 8 (PAX3g and PAX3h) and mRNAs containing 4 or 5 exons (PAX3a and PAX3b). In limited studies comparing isoform expression, PAX3d is expressed at the highest levels. From a functional standpoint, PAX3c, PAX3d, and PAX3h stimulate activities such as cell growth whereas PAX3e and PAX3g inhibit these activities, and PAX3a and PAX3b show no activity or inhibit these endpoints.
A common alternative splice affecting the PAX3 mRNA involves the sequence CAG at the 5’ end of exon 3. This splice either includes or excludes these three bases, thus resulting in the presence or absence of a glutamine residue in the paired box motif. Limited sequencing studies of full-length human cDNAs identified this splicing event as a variant of the PAX3d isoform, and this spliced isoform has been separately termed the PAX3i isoform. The Q+ and Q- isoforms of PAX3 are generally co-expressed in cells. At the functional level, the Q+ isoform shows similar or less DNA binding and transcriptional activation than the Q- isoform.
Protein structure and function.
PAX3 encodes a transcription factor with an N-terminal DNA binding domain consisting of a paired box (PD) encoded by exons 2, 3, and 4, and an octapeptide and complete homeodomain (HD) encoded by exons 5 and 6. In addition, the PAX3 protein has a C-terminal transcriptional activation domain encoded by exons 7 and 8. The highly conserved PD consists of a 128 amino acid region that binds to DNA sequences related to the TCACGC/G motif. The HD motif usually consists of 60 amino acids and binds to sequences containing a TAAT core motif. The combination of these two DNA binding domains enable the PAX3 protein to recognize longer sequences containing PD and HD binding sites. In the C-terminus of PAX3, there is a proline, serine and threonine (PST)-rich region measuring 78 amino acids that functions to stimulate transcriptional activity. There are also transcriptional repression domains in the HD and N-terminal region (including the first half of the PD) that repress the C-terminal transcriptional activation domain.
PAX3 functions as a transcriptional activator for most target genes, but also may repress a smaller subset of target genes. These expression changes are effected through binding of PAX3 to specific recognition sites, which are situated in various genomic locations. Some binding sites are located in or near target genes, such as the 5’ promoter, first intron and 3’ untranslated region. A substantial number of PAX3 binding sites are located at larger distances upstream and downstream of target genes. Among the PAX3 target genes, there is one group associated with muscle development and a second group associated with neural and melanocyte development. The proteins encoded by these target genes regulate various functional activities in these lineages, including differentiation, proliferation, migration, adhesion, and apoptosis.
PAX3 interacts with other nuclear proteins, which modulate PAX3 transcriptional activity. Dimerization of PAX3 with another PAX3 molecule or a PAX7 molecule enables binding to a palindromic HD binding site (TAATCAATTA). Interaction of PAX3 with other transcription factors (such as SOX10) or chromatin factors (such as PAX3/7BP) enables synergistic activation of PAX3 target genes. In contrast, binding of PAX3 to co-repressors, such as calmyrin, inhibits activation of PAX3 target genes. These co-repressors may function by altering chromatin structure at target genes, inhibiting PAX3 recognition of its DNA binding site or directly altering PAX3 transcriptional activity.
Finally, PAX3 protein expression and function can be modulated by post-translational modifications. PAX3 can be phosphorylated at serines 201, 205 and 209 by kinases such as GSK3b, which in some settings will increase PAX3 protein stability. In addition, PAX3 can also undergo ubiquitination and acetylation at lysines 437 and 475, which regulates protein stability and function.
Table 1. Representative PAX3 transcriptional target genes.
Expression during development.
During development, one of the major lineages expressing Pax3 is the skeletal muscle lineage. Pax3 expression is first seen in the pre-somitic paraxial mesoderm, and then ultimately becomes restricted to the dermomyotome, which forms from the dorsal region of the somites. To form skeletal muscle in central body segments, PAX3-expressing cells detach from the dermomyotome and then Pax3 expression is turned off as Myf5 and MyoD1 expression is activated. To form other skeletal muscles, Pax3-expressing cells detach from the dermomyotome and migrate to more distant sites, such as the limbs and diaphragm. A subset of these Pax3-expressing dermomyotome-derived cells also serves as an ongoing progenitor pool for skeletal muscle growth during fetal development. During later developmental stages, myogenic precursors expressing Pax3 and/or Pax7 form satellite cells within the skeletal muscle, which contribute to postnatal muscle growth and muscle regeneration. These adult satellite cells remain quiescent until injury occurs, and then are stimulated to divide and regenerate the injured muscle.
Pax3 is also involved in the development of the nervous system. Expression of Pax3 is first detected in the dorsal region of the neural groove and, as this neural groove deepens to form the neural tube, Pax3 is expressed in the dorsal portion of the neural tube. As the neural tube enlarges, Pax3 expression is localized to proliferative cells in the inner ventricular zone and then this expression is turned off as these cells migrate to more superficial regions. Pax3 is expressed along the length of the neural tube and throughout much of the developing brain, and this expression is subsequently turned off during later developmental stages in a rostral to caudal direction.
During early development, Pax3 expression also occurs at the lateral and posterior margins of the neural plate, which is the region from which the neural crest arises. Pax3 is later expressed by various cell types and structures arising from the neural crest, such as melanoblasts, Schwann cell precursors, and dorsal root ganglia. In addition, Pax3-expressing cells derived from the neural crest contribute to the formation of other structures, such as the inner ear, mandible and maxilla.
Germline mutations in disease.
Germline mutations of the Pax3 gene cause the splotch phenotype in mice. At the molecular level, this phenotype is caused by point mutations or deletions that alter or abolish Pax3 transcriptional function. In the heterozygous state, the splotch phenotype is characterized by white patches in the belly, tail and feet. These white spots are attributed to localized deficiencies in pigment-forming melanocytes resulting from neural crest cell defects. In the homozygous state, these Pax3 mutations cause embryonic lethality, which is associated with prominent neural tube closure defects and abnormalities of neural crest-derived structures, such as melanocytes, dorsal root ganglia and enteric ganglia. Heart malformations also result from the loss of cardiac neural crest cells, which normally contribute to the cardiac outflow tract and innervation of the heart. Finally, limb musculature does not develop in the homozygotes and axial musculature demonstrates varying abnormalities. These myogenic effects are caused by increased cell death of myogenic precursors in the dermomyotome and diminished migration from the dermomyotome.
Germline mutations of the PAX3 gene occur in the human disease Waardenburg syndrome, which consists of four autosomal dominant genetic disorders (WS1, WS2, WS3 and WS4). Of the four subtypes, WS1 and WS3 are usually caused by PAX3 mutations. All four subtypes are characterized by hearing loss, eye abnormalities and pigmentation disorders. In addition, WS1 is frequently associated with a midfacial alteration called dystopia canthorum, while WS3 (Klein-Waardenburg syndrome) is frequently distinguished by musculoskeletal abnormalities affecting the upper limbs. Most WS1 cases are caused by heterozygous PAX3 mutations while WS3 is caused by either partial or total deletion of PAX3 and contiguous genes or by smaller PAX3 mutations in the heterozygous or homozygous state. These PAX3 mutations in WS1 and WS3 include missense, nonsense and splicing mutations; small insertions; and small or gross deletions. Though these changes are usually not recurrent, the mutations generally occur in exons 2 through 6 with exon 2 mutations being most common. As these exons encode the paired box and homeodomain, these mutations often affect DNA binding function.
Mutations in human cancer.
Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue sarcoma that occurs in children and is usually characterized by a recurrent t(2;13)(q35;q14) chromosomal translocation. This 2;13 translocation breaks and rejoins portions of the PAX3 and FOXO1 genes to generate a PAX3-FOXO1 fusion gene that expresses a PAX3-FOXO1 fusion transcript encoding a PAX3-FOXO1 fusion protein. PAX3 and FOXO1 encode transcription factors, and the translocation results in a fusion transcription factor containing the N-terminal PAX3 DNA-binding domain and the C-terminal FOXO1 transactivation domain. A smaller subset of ARMS cases is associated with less common fusions of PAX7 to FOXO1 or rare fusions of PAX3 to other transcription factors, such as NCOA1. Compared to the wild-type PAX3 protein, the PAX3-FOXO1 fusion protein more potently activates PAX3 target genes. In ARMS cells, PAX3-FOXO1 usually functions as a transcriptional activator and excessively increases expression of downstream target genes. In addition, PAX3-FOXO1 binds along with MYOD1, MYOG and MYCN as well as chromatin structural proteins, such as CHD4 and BRD4, to contribute to the formation of super enhancers in the vicinity of a subset of these target genes. These dysregulated target genes contribute to tumorigenesis by altering signaling pathways that affect proliferation, cell death, myogenic differentiation, and migration.
A t(2;4)(q35;q31.1) chromosomal translocation that fuses the PAX3 and MAML3 genes occurs in biphenotypic sinonasal sarcoma (BSNS), a low-grade adult malignancy associated with both myogenic and neural differentiation. MAML3 encodes a transcriptional coactivator involved in Notch signaling. The PAX3-MAML3 fusion juxtaposes the N-terminal PAX3 DNA binding domain with the C-terminal MAML3 transactivation domain to create another potent activator of target genes with PAX3 binding sites. Of note, PAX3 is rearranged without MAML3 involvement in a smaller subset of BSNS cases, and some of these variant cases contain a PAX3-NCOA1 or PAX3-FOXO1 fusion. Though PAX3-FOXO1 and PAX3-NCOA1 fusions can be formed in both ARMS and BSNS, there are differences in the pattern of activated downstream target genes suggesting that the cell environment has an important role in modulating the output of these fusion transcription factors.
In addition to tumors with PAX3-related fusion genes, there are several other tumor categories that express the wild-type PAX3 gene. The presence of PAX3 expression in some tumors can be explained by their derivation from developmental lineages normally expressing wild-type PAX3. For example, PAX3 is expressed in cancers associated with neural tube-derived lineages, (e.g., glioblastoma), neural crest-derived lineages (e.g., melanoma) and myogenic lineages (e.g., embryonal rhabdomyosarcoma). However, PAX3 is also expressed in other cancer types without a clear relationship to a PAX3-expressing developmental lineages, such as breast carcinoma and osteosarcoma. In these wild-type PAX3-expressing cancers, PAX3 function impacts on the control of proliferation, apoptosis, differentiation and motility. Therefore, wild-type PAX3 exerts a regulatory role in tumorigenesis and tumor progression, which may be related to its role in normal development.


HldE

HldE may refer to:


N-acetylglutamate synthetase

N-acetylglutamate synthetase may refer to:


Asx motif

The Asx motif is a commonly occurring feature in proteins and polypeptides. It consists of four or five amino acid residues with either aspartate or asparagine as the first residue (residue i). It is defined by two internal hydrogen bonds. One is between the side chain oxygen of residue i and the main chain NH of residue i+2 or i+3; the other is between the main chain oxygen of residue i and the main chain NH of residue i+3 or i+4. Asx motifs occur commonly in proteins and polypeptides.

When one of the hydrogen bonds is between the main chain oxygen of residue i and the side chain NH of residue i+3 the motif incorporates a beta turn. When one of the hydrogen bonds is between the side chain oxygen of residue i and the main chain NH of residue i+2 the motif incorporates an Asx turn.
As with Asx turns, a significant proportion of Asx motifs occur at the N-terminus of an alpha helix with the Asx as the N cap residue. Asx motifs have thus often been described as helix capping features.
A related motif is the ST motif which has serine or threonine as the first residue.


Arcapillin

Arcapillin is an α-glucosidase and protein tyrosine phosphatase inhibitor isolated from "Artemisia capillaris".


HaloTag

HaloTag is a self-labeling protein tag. It is a 297 residue peptide (33 kDa) derived from a bacterial enzyme, designed to covalently bind to a synthetic ligand. The bacterial enzyme can be fused to various proteins of interest. The synthetic ligand is chosen from a number of available ligands in accordance with the type of experiments to be performed. This bacterial enzyme is a haloalkane dehalogenase, which acts as a hydrolase and is designed to facilitate visualization of the subcellular localization of a protein of interest, immobilization of a protein of interest, or capture of the binding partners of a protein of interest within its biochemical environment. The HaloTag is composed of two covalently bound segments including a haloalkane dehalogenase and a synthetic ligand of choice. These synthetic ligands consist of a reactive chloroalkane linker bound to a functional group. Functional groups can either be biotin (can be used as an affinity tag) or can be chosen from five available fluorescent dyes including Coumarin, Oregon Green, Alexa Fluor 488, diAcFAM, and TMR. These fluorescent dyes can be used in the visualization of either living or chemically fixed cells.
Mechanism.
The HaloTag is a hydrolase, which has a genetically modified active site, which specifically binds the reactive chloroalkane linker and has an increased rate of ligand binding. The reaction that forms the bond between the protein tag and chloroalkane linker is fast and essentially irreversible under physiological conditions due to the terminal chlorine of the linker portion. In the aforementioned reaction, nucleophilic attack of the chloroalkane reactive linker causes displacement of the halogen with an amino acid residue, which results in the formation of a covalent alkyl-enzyme intermediate. This intermediate would then be hydrolyzed by an amino acid residue within the wild-type hydrolase. This would lead to regeneration of the enzyme following the reaction. However, in the modified haloalkane dehalogenase (HaloTag), the reaction intermediate cannot proceed through a subsequent reaction because it cannot be hydrolyzed due to the mutation in the enzyme. This causes the intermediate to persist as a stable covalent adduct with which there is no associated back reaction.
Uses.
 HaloTagged fusion proteins can be expressed using standard recombinant protein expression techniques. Furthermore, there are several commercial vectors available that just require insertion of a gene of interest. Since bacterial dehalogenases are relatively small and the reactions described above are foreign to mammalian cells, there is no interference by endogenous mammalian metabolic reactions. Once the fusion protein has been expressed, there is a wide range of potential areas of experimentation including enzymatic assays, cellular imaging, protein arrays, determination of sub-cellular localization, and many additional possibilities.


Cerevisterol

Cerevisterol (5α-ergosta-7,22-diene-3β,5,6β-triol) is a sterol. Originally described in the 1930s from the yeast "Saccharomyces cerevisiae", it has since been found in several other fungi and, recently, in deep water coral. Cerevisterol has some "in vitro" bioactive properties, including cytotoxicity to some mammalian cell lines.
Discovery and properties.
Cerevisterol was first discovered in 1928 as a component of crude yeast ("Saccharomyces cerevisiae") sterols remaining from the manufacture of the related ergosterol. Chemists Edna M. Honeywell and Charles E. Bills purified the compound and reported some of its properties in a 1932 publication. They noted its high melting point (265.3 °C) relative to other sterols, and insolubility in the organic solvent hexane. These characteristics facilitated its purification, and they were able to obtain of cerevisterol from of dry yeast. The following year, they determined its chemical formula to be C26H46O3, with two double bonds, and with two of the oxygen molecules occurring in hydroxyl groups.
Its structure was determined in 1954 by comparison with a sample that was chemically synthesized from ergosterol. Purified cerevisterol has the form of a white amorphous solid. When crystallized in ethyl alcohol, it forms elongated prisms, while crystallization in acetone or ethyl acetate produces broad hexagonal prisms. Its UV absorption spectrum shows a maximum at about 248 nm. Cerevisterol is a stable molecule, showing no discoloration or change in melting point even after several weeks of exposure to light and air.
Occurrence.
Cerevisterol is widely distributed in the fungal kingdom. In the division Basidiomycota, it occurs in several members of the fungal family Boletaceae, the edible mushrooms "Cantharellus cibarius", "Volvariella volvacea", "Pleurotus sajor-caju", "Laetiporus sulphureus", and "Suillus luteus", in the milk mushroom "Lactarius hatsudake", and the coral fungus "Ramaria botrytis". In the division Ascomycota, it has been reported in "Auricularia polytricha", "Bulgaria inquinans", "Engleromyces goetzei", "Acremonium luzulae", and "Pencillium herquei", as well as the lichens "Ramalina hierrensis" and "Stereocaulon azoreum". It has also been found in the endophytes "Alternaria brassicicola", "Fusarium oxysporum", and a strain of "Gliocladium", and the deep-sea fungus "Aspergillus sydowi". In 2013, the sterol was reported in the South China Sea gorgonian coral "Muriceoopsis flavida". A 9-hydroxylated analogue of cerevisterol was found in "R. botrytis". A modified version of the compound, (22"E", 24"R")-cerevisterol, has been reported from the coral "Subergorgia mollis". It was shown to be moderately cytotoxic to embryos of the zebrafish "Danio rerio".
Bioactivity.
Cerevisterol inhibits the eukaryotic enzyme DNA polymerase alpha, and it is also a potent inhibitor of NF-kappa B activation. The sterol is cytotoxic to mouse P388 leukemia cells and A549 human alveolar epithelial cells grown in culture.


Lactucopicrin

Lactucopicrin (Intybin) is a bitter substance that has a sedative and analgesic effect, acting on the central nervous system. It is a sesquiterpene lactone, and is a component of lactucarium, derived from the plant "Lactuca virosa" (wild lettuce), as well as being found in some related plants such as "Cichorium intybus". It is also found in dandelion coffee.
As well as their traditional use as sedatives and analgesics, these plants have also been used as antimalarials, and both lactucin and lactucopicrin have demonstrated antimalarial effects "in vitro". Lactucopicrin has also been shown to act as an acetylcholinesterase inhibitor.


HslVU

The heat shock proteins HslV and HslU (HslVU complex; also known as ClpQ and ClpY respectively, or ClpQY) are expressed in many bacteria such as "E. coli" in response to cell stress. The hslV protein is a protease and the hslU protein is an ATPase; the two form a symmetric assembly of four stacked rings, consisting of an hslV dodecamer bound to an hslU hexamer, with a central pore in which the protease and ATPase active sites reside. The hslV protein degrades unneeded or damaged proteins only when in complex with the hslU protein in the ATP-bound state. HslV is thought to resemble the hypothetical ancestor of the proteasome, a large protein complex specialized for regulated degradation of unneeded proteins in eukaryotes, many archaea, and a few bacteria. HslV bears high similarity to core subunits of proteasomes.
Genetics.
Both proteins are encoded on the same operon within the bacterial genome. Unlike many eukaryotic proteasomes, which have several different peptide substrate specificities, hslV has a specificity similar to that of chymotrypsin; hence it is inhibited by proteasome inhibitors that specifically target the chymotrypsin site in eukaryotic proteasomes. Although the HslVU complex is stable on its own, some evidence suggests that the complex is formed "in vivo" in a substrate-induced manner due to a conformational change in the hslU-substrate complex that promotes hslV binding.
HslV and hslU genes have also been identified in some eukaryotes, although these also require the constitutively expressed proteasome for survival. These eukaryotic HslVU complexes assemble to apparently functional units, suggesting that these eukaryotes have both functional proteasomes and functional hslVU systems.
Regulation.
The promoter region of the operon encoding HslU and HslV contains a stem-loop structure which is necessary for gene expression. This structure contributes to mRNA stability.
Motifs in peptide unfolding.
A four-amino acid sequence motif - GYVG, glycine-tyrosine-valine-glycine - conserved in hslU ATPases and located on the inner surface of the assembled pore dramatically accelerates the degradation of some proteins, and is required for the degradation of others. However, these motifs are not necessary for the degradation of short peptides and play no direct role in hydrolysis, suggesting that their major role is in unfolding the native state structure of the substrate and transferring the resulting disordered polypeptide chain to the hslV subunits for degradation. These motifs also influence the assembly of the complex. Translocation is also facilitated by the C-terminal tails of the HslU subunits, which form a gate closing off the proteolytic active sites in the central pore until a substrate has been bound and unfolded.
Mechanism.
The basic mechanism by which the hslVU complex undertakes proteolytic substrate degradation is essentially the same as that observed in the eukaryotic proteasome, catalyzed by Nactive-site threonine residues. Both are members of the T1 family. It is inhibited by enzyme inhibitors that covalently bind the threonine. Like the proteasome, hslU must bind ATP in a magnesium-dependent manner before substrate binding and unfolding can occur.


2-Epimerase

2-Epimerase can refer one of to several enzymes:


ATP cone

In molecular biology, the ATP-cone is an evolutionarily mobile, ATP-binding regulatory domain which is found in a variety of proteins including ribonucleotide reductases, phosphoglycerate kinases and transcriptional regulators.
In ribonucleotide reductase protein R1 from "Escherichia coli" this domain is located at the N terminus, and is composed mostly of helices. It forms part of the allosteric effector region and contains the general allosteric activity site in a cleft located at the tip of the N-terminal region. This site binds either ATP (activating) or dATP (inhibitory), with the base bound in a hydrophobic pocket and the phosphates bound to basic residues. Substrate binding to this site is thought to affect enzyme activity by altering the relative positions of the two subunits of ribonucleotide reductase.


Protein tandem repeats

An array of protein tandem repeats is defined as several (at least two) adjacent copies having the same or similar sequence motifs. These periodic sequences are generated by internal duplications in both coding and non-coding genomic sequences. Repetitive units of protein tandem repeats are considerably diverse, ranging from the repetition of a single amino acid to domains of 100 or more residues.
"Repeats" in proteins.
In proteins, a "repeat" is any sequence block that returns more than one time in the sequence, either in an identical or a highly similar form. The degree of similarity can be highly variable, with some repeats maintaining only a few conserved amino acid positions and a characteristic length. Highly degenerate repeats can be very difficult to detect from sequence alone. Structural similarity can help to identify repetitive patterns in sequence.
Structure.
Repetitiveness does not in itself indicate anything about the structure of the protein. As a "rule of thumb", short repetitive sequences (e.g. those below the length of 10 amino acids) may be intrinsically disordered, and not part of any folded protein domains. Repeats that are at least 30 to 40 amino acids long, are far more likely to be folded as part of a domain. Such long repeats are frequently indicative of the presence of a solenoid domain in the protein.
Approximately half of the tandem repeat regions have intrinsically disordered conformation being naturally unfolded. Examples of disordered repetitive sequences include the 7-mer peptide repeats found in the RPB1 subunit of RNA polymerase II, or the tandem beta-catenin or axin binding linear motifs in APC (adenomatous polyposis coli).
The other half of the regions with the stable 3D structure has a plethora of shapes and functions. Examples of short repeats exhibiting ordered structures include the three-residue collagen repeat or the five-residue pentapeptide repeat that forms a beta helix structure.
Classification.
Depending on the length of the repetitive units, their protein structures can be subdivided into five classes:
Function.
Some well-known examples of proteins with tandem repeats are collagen, which plays a key role in the arrangement of the extracellular matrix; alpha-helical coiled coils having structural and oligomerization functions; leucine-rich repeat proteins, which specifically bind a number of globular proteins by their concave surfaces; and zinc-finger proteins, which regulate the expression of genes by binding DNA.
Tandem repeat proteins frequently function as protein-protein interaction modules. The WD40 repeat is a prime example of this function.
Distribution in proteomes.
Tandem repeats are ubiquitous in proteomes and occur in at least 14% of all proteins. For example, they are present in almost every third human protein and even in every second protein from Plasmodium falciparum or Dictyostelium discoideum. Tandem repeats with short repetitive units (especially homorepeats) are more frequent than others.
Annotation methods.
Protein tandem repeats can be either detected from sequence or annotated from structure. Specialized methods were built for the identification of repeat proteins.
Sequence-based strategies, based on homology search or domain assignment ,mostly underestimate TRs due to the presence of highly degenerate repeat units. A recent study to understand and improve Pfam coverage of the human proteome showed that five among the ten largest sequence clusters not annotated with Pfam are repeat regions. Alternatively, methods requiring no prior knowledge for the detection of repeated substrings can be based on self-comparison, clustering or hidden Markov models. Some others rely on complexity measurements or take advantage of meta searches to combine outputs from different sources.
Structure-based methods instead take advantage of the modularity of available PDB structures to recognize repetitive elements.


Biopterin

Biopterins are pterin derivatives which function as endogenous enzyme cofactors in many species of animals and in some bacteria and fungi. Biopterins act as cofactors for aromatic amino acid hydroxylases (AAAH), which are involved in the synthesis of a number of neurotransmitters including dopamine, norepinephrine, epinepherine, and serotonin, along with several trace amines. Nitric oxide synthesis also uses biopterin derivatives as cofactors. In humans, tetrahydrobiopterin is the endogenous cofactor for AAAH enzymes.
Compounds.
Biopterin compounds found within the body include BH4, the free radical BH3, and BH2 (also a free radical).
Synthesis.
Biopterin synthesis occurs through two principal pathways; the de novo pathway involves three enzymatic steps and proceeds from GTP, while the salvage pathway converts sepiapterin to biopterin. BH4 is the principal active cofactor, and a recycling pathway converts BH2 to BH4.
Biopterin disorders.
A number of disorders of biopterin regulation exist.
Single-gene defects affecting the gene GCH1 block the first step in biopterin synthesis, and lead to dopamine-responsive dystonia, also known as Segawa's syndrome. This is due to the role of BH4 in synthesising neurotransmitters, including Dopamine, and is treated with supplementation with levodopa, which does not require BH4 for conversion to dopamine. GCH1 defects are autosomal dominant, meaning that only one defective gene copy is required for the condition to occur. Mouse gene knockout models that block biopterin synthesis completely die shortly after birth due to their inability to produce catecholamines and neurotransmitters.
Biopterin synthesis disorders are also a cause of hyperphenylalaninemia; phenylalanine metabolism requires BH4 as a cofactor.
External links.
WiseGeek. (2012). What is biopterin?. Retrieved from http://www.wisegeek.com/what-is-biopterin.htm


Stauprimide

Stauprimide is a semi-synthetic analog of the staurosporine family of indolocarbazoles. Stauprimide was first published in 1994 as part of an extensive structure-activity investigation to improve the selective inhibition of protein kinase C as a potential antitumor agent. More recently, stauprimide has been shown to increase the efficiency of the directed differentiation of mouse and human embryonic stem cells in synergy with defined extracellular signaling cues. Stauprimide interacts with NME2 (PUF) transcription factor to down-regulate c-Myc expression, leading to differentiation of stem cells.


Type XXVII collagen

Type XXVII collagen is the protein predicted to be encoded by COL27A1. It was first described by Dr. James M. Pace and his colleagues at the University of Washington. It is related to the fibrillar collagens: type II, type XI, and type XXIV. Current research suggests that it is made by cartilage during skeletal development.


Cofactor transferase family

In molecular biology, the Cofactor transferase family is a family of protein domains that includes biotin protein ligases, lipoate-protein ligases A, octanoyl-(acyl carrier protein):protein N-octanoyltransferases, and lipoyl-protein:protein N-lipoyltransferases. The metabolism of the cofactors Biotin and lipoic acid share this family. They also share the target modification domain (), and the sulfur insertion enzyme ().
Biotin protein ligase (BPL) is the enzyme responsible for attaching biotin to a specific lysine at the biotin carboxyl carrier protein. Each organism likely has only one BPL protein. Biotin attachment is a two step reaction that results in the formation of an amide linkage between the carboxyl group of biotin and the epsilon-amino group of the modified lysine. Biotin attachment is required for biotin biosynthesis and utilization of free biotin.
Lipoate-protein ligase catalyses the formation of an amide linkage between lipoic acid and a specific lysine residue of the lipoyl domain of lipoate dependent enzymes. They are required for the utilization of free lipoic acid.
Octanoyl-(acyl carrier protein):protein N-octanoyltransferases, or octanoyltransferases, are required for lipoic acid biosynthesis. They transfer octanoate from the acyl carrier protein (ACP), part of fatty acid biosynthesis, to the specific lysine residue of lipoyl domains. Two octanoyltransferase isozymes exist in this superfamily.
Lipoyl-protein:protein N-lipoyltransferases, or lipoylamidotransferases, are required for lipoic acid metabolism in some organisms. They transfer lipoic acid or octanoate from lipoyl domains and transfer to other lipoyl domains. In Bacillus subtilis, the transfer is from the glycine cleavage system H protein, GcvH, to other lipoyl domains. This is because the octanoyltransferase of "B. subtilis" is specific for GcvH.
Structure.
Octanoyltransferases and lipoyl-amidotransferases are single domain enzymes. Characterized lipoate protein ligases require an additional accessory domain () to adenylate the acyl substrate. Biotin protein ligases have an additional C-terminal domain which participates in biotin adenylation and dimerization. Biotin protein ligases may also have an additional N-terminal domain required for DNA binding, although this domain is not always present.


D-malate dehydrogenase (decarboxylating)

In enzymology, a D-malate dehydrogenase (decarboxylating) () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are (R)-malate and NAD+, whereas its 3 products are pyruvate, CO2, and NADH.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is (R)-malate:NAD+ oxidoreductase (decarboxylating). Other names in common use include D-malate dehydrogenase, D-malic enzyme, bifunctional L(+)-tartrate dehydrogenase-D(+)-malate (decarboxylating). This enzyme participates in butanoate metabolism.


Pentapeptide repeat

Pentapeptide repeats are a family of sequence motifs found in multiple tandem copies in protein molecules. Pentapeptide repeat proteins are found in all species, but they are found in many copies in cyanobacterial genomes. The repeats were first identified by Black and colleagues in the hglK protein. The later Bateman "et al." showed that a large family of related pentapeptide repeat proteins existed. The function of these repeats is uncertain in most proteins. However, in the MfpA protein a DNA gyrase inhibitor it has been suggested that the pentapeptide repeat structure mimics the structure of DNA. The repeats form a regular right handed four sided beta helix structure known as the Rfr-fold.
Sequence features.
The pentapeptide repeat is a feature seen in protein sequence. It can be approximately described using the 1-letter amino acid code as A(D/N)LXX, where X can be any amino acid . This repeating sequence can be seen in multiple sequence alignments and dot plots of proteins such as HglK. The central position in the pentapeptide repeat is usually a leucine and has been designated as position "i". The two previous positions are known as "i"-1 and "i"-2. Position i-2 is usually an alanine. The two subsequent positions are denoted "i"+1 and "i"+2. The side chains of positions "i"-2 and "i" point into the hydrophobic interior of the protein while the side chains of positions "i"-1, "i"+1 and "i"+2 are exposed on the surface of the proteins.
Structure.
Pentapeptide repeats were initially predicted from sequence to possess a right handed beta helix with three sides. The first crystal structure of a pentapeptide repeat protein was the MfpA protein solved by Hegde and colleagues. It showed that pentapeptide repeat proteins (PRPs) possessed a four sided beta helix structure. Four repeats make up one turn of a solenoid like structure. The structures of eight different proteins have been solved to date.


CELA2A

Chymotrypsin-like elastase family member 2A is an enzyme that in humans is encoded by the "CELA2A" gene.
Function.
Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Like most of the human elastases, elastase 2A is secreted from the pancreas as a zymogen. In other species, elastase 2A has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. Clinical literature that describes human elastase 1 activity in the pancreas is actually referring to elastase 2A.


NAAA (gene)

NAAA (gene) may refer to:


Preproenzyme

A preproenzyme is an enzyme with two additional characteristics: "pre" refers to a signal sequence (signal peptide) which directs the enzyme to a specific organelle or subcellular localization; "pro" indicates that the enzyme is present in an inactive form and requires modification (e.g. cleavage) for activation.