Beta-ketoacyl-ACP synthase

In molecular biology, Beta-ketoacyl-ACP synthase , is an enzyme involved in fatty acid synthesis. It typically uses malonyl-CoA as a carbon source to elongate ACP-bound acyl species, resulting in the formation of ACP-bound β-ketoacyl species such as acetoacetyl-ACP.
Beta-ketoacyl-ACP synthase is a highly conserved enzyme that is found in almost all life on earth as a domain in fatty acid synthase (FAS). FAS exists in two types, aptly named type I and II. In animals, fungi, and lower eukaryotes, Beta-ketoacyl-ACP synthases make up one of the catalytic domains of larger multifunctional proteins (Type I), whereas in most prokaryotes as well as in plastids and mitochondria, Beta-ketoacyl-ACP synthases are separate protein chains that usually form dimers (Type II).
Beta-ketoacyl-ACP synthase III, perhaps the most well known of this family of enzymes, catalyzes a Claisen condensation between acetyl CoA and malonyl ACP. The image below reveals how CoA fits in the active site as a substrate of synthase III.
Beta-ketoacyl-ACP synthases I and II only catalyze acyl-ACP reactions with malonyl ACP. Synthases I and II are capable of producing long-chain acyl-ACPs. Both are efficient up to acyl-ACPs with a 14 carbon chain, at which point synthase II is the more efficient choice for further carbon additions. Type I FAS catalyzes all the reactions necessary to create palmitic acid, which is a necessary function in animals for metabolic processes, one of which includes the formation of sphingosines.
Beta-ketoacyl-ACP synthase is found as a component of a number of enzymatic systems, including fatty acid synthetase (FAS); the multi-functional 6-methysalicylic acid synthase (MSAS) from "Penicillium patulum", which is involved in the biosynthesis of a polyketide antibiotic; polyketide antibiotic synthase enzyme systems; "Emericella nidulans" multifunctional protein Wa, which is involved in the biosynthesis of conidial green pigment; "Rhizobium" nodulation protein nodE, which probably acts as a beta-ketoacyl synthase in the synthesis of the nodulation Nod factor fatty acyl chain; and yeast mitochondrial protein CEM1.
Structure.
Beta-ketoacyl synthase contains two protein domains. The active site is located between the N- and C-terminal domains. The N-terminal domain contains most of the structures involved in dimer formation and also the active site cysteine. Residues from both domains contribute to substrate binding and catalysis
In animals and in prokaryotes, beta-ketoacyl-ACP synthase is a domain on type I FAS, which is a large enzyme complex that has multiple domains to catalyze multiple different reactions. Analogously, beta-ketoacyl-ACP synthase in plants is found in type II FAS; note that synthases in plants have been documented to have a range of substrate specificities. The presence of similar ketoacyl synthases present in all living organisms point to a common ancestor. Further examination of beta-ketoacyl-ACP synthases I and II of E. coli revealed that both are homodimeric, but synthase II is slightly larger. However, even though they are both involved in fatty acid metabolism, they also have highly divergent primary structure. In synthase II, each subunit consists of a five-stranded beta pleated sheet surrounded by multiple alpha helices, shown in the image on the left. The active sites are relatively close, only about 25 angstroms apart, and consist of a mostly hydrophobic pocket. Certain experiments have also suggested the presence of “fatty acid transport tunnels” within the beta-ketoacyl-ACP synthase domain that lead to one of many “fatty acid cavities”, which essentially acts as the active site.
Mechanism.
Beta-ketoacyl-synthase’s mechanism is a topic of debate among chemists. Many agree that Cys171 of the active site attacks acetyl ACP's carbonyl, and, like most enzymes, stabilizes the intermediate with other residues in the active site. ACP is subsequently eliminated, and it deprotonates His311 in the process. A thioester is then regenerated with the cysteine in the active site. Decarboxylation of a malonyl CoA that is also in the active site initially creates an enolate, which is stabilized by His311 and His345. The enolate tautomerizes to a carbanion that attacks the thioester of the acetyl-enzyme complex. Some sources speculate that an activated water molecule also resides in the active site as a means of hydrating the released CO2 or of attacking C3 of malonyl CoA. Another proposed mechanism considers the creation of a tetrahedral transition state. The driving force of the reaction comes from the decarboxylation of malonyl ACP; the energy captured in that bond technically comes from ATP, which is what is initially used to carboxylate acetyl CoA to malonyl CoA.
Biological function.
The main function of beta-ketoacyl-ACP synthase is to produce fatty acids of various lengths for use by the organism. These uses include energy storage and creation of cell membranes. Fatty acids can also be used to synthesize prostaglandins, phospholipids, and vitamins, among many other things. Further, palmitic acid, which is created by the beta-ketoacyl-synthases on type I FAS, is used in a number of biological capacities. It is a precursor of both stearic and palmitoleic acids. Palmitoleic can subsequently be used to create a number of other fatty acids. Palmitic acid is also used to synthesize sphingosines, which play a role in cell membranes.
Clinical significance.
The different types of beta-ketoacyl-ACP synthases in type II FAS are called FabB, FabF, and FabH synthases. FabH catalyzes the quintessential ketoacyl synthase reaction with malonyl ACP and acetyl CoA. FabB and FabF catalyze other related reactions. Given that their function is necessary for proper biological function surrounding lipoprotein, phospholipid, and lipopolysaccharide synthesis, they have become a target in antibacterial drug development. In order to adapt to their environment, bacteria alter the phospholipid composition of their membranes. Inhibiting this pathway may thus be a leverage point in disrupting bacterial proliferation. By studying Yersinia pestis, which causes bubonic, pneumonic, and septicaemic plagues, researchers have shown that FabB, FabF, and FabH can theoretically all be inhibited by the same drug due to similarities in their binding sites. However, such a drug has not yet been developed. Cerulenin, a molecule that appears to inhibit by mimicking the “condensation transition state” can only inhibit B or F, but not H. Another molecule, thiolactomycin, which mimics malonyl ACP in the active site, can ony inhibit FabB. Lastly, platensimycin also has possible antibiotic use due to its inhibition of FabF.
These types of drugs are highly relevant. For example, Y. pestis was the main agent in the Justinian Plague, Black Death, and the modern plague. Even within the last five years, China, Peru, and Madagascar all experienced an outbreak of infection by Y. pestis. If it is not treated within 24 hours, it normally results in death. Furthermore, there is worry that it can now be used as a possible biological warfare weapon.
Unfortunately, many drugs that target prokaryotic beta-ketoacyl-synthases carry many side effects. Given the similarities between prokaryotic ketoacyl synthases and mitochondrial ones, these types of drugs tend to unintentionally also act upon mitochondrial synthases, leading to many biological consequences for humans.
Industrial applications.
Recent efforts in bioengineering include engineering of FAS proteins, which includes beta-ketoacyl-ACP synthase domains, in order to favor the synthesis of branched carbon chains as a renewable energy source. Branched carbon chains contain more energy and can be used in colder temperatures because of their lower freezing point. Using E. coli as the organism of choice, engineers have replaced the endogenous FabH domain on FAS, which favors unbranched chains, with FabH versions that favor branching due to their high substrate specificity for branched acyl-ACPs.


Alkylglycerophosphoethanolamine phosphodiesterase

In enzymology, an alkylglycerophosphoethanolamine phosphodiesterase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 1-alkyl-sn-glycero-3-phosphoethanolamine and H2O, whereas its two products are 1-alkyl-sn-glycerol 3-phosphate and ethanolamine.
This enzyme belongs to the family of hydrolases, specifically those acting on phosphoric diester bonds. The systematic name of this enzyme class is 1-alkyl-sn-glycero-3-phosphoethanolamine ethanolaminehydrolase. This enzyme is also called lysophospholipase D. This enzyme participates in ether lipid metabolism.
Structural studies.
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code .


Dual-specificity phosphatase

Dual-specificity phosphatase (DUSP; DSP) is a form of phosphatase that can act upon tyrosine or serine/threonine residues.
There are several families of dual-specificity phosphatase enzymes in mammals. All share a similar catalytic mechanism, by which a conserved cysteine residue forms a covalent intermediate with the phosphate group to be eliminated. The residues surrounding their catalytic core obey a rather strict consensus: His-Cys-x-x-x-x-x-Arg-Ser. The serine side chain and an additional conserved aspartate play a central role in the elimination of the Cys-linked intermediate, thus completing their enzymatic cycle. The main difference between tyrosine-specific phosphatases and dual-specificity phosphatases lies in the width of the latter enzymes' catalytic pocket: thus they can accommodate phosphorylated serine or threonine side chains as well as phosphorylated tyrosines.
Classification.
The human genome encodes at least 61 different DUSP proteins. The following major groups or families of DUSPs were identified:
There are three members of this family (SSH1L, SSH2L and SSH3L) with broad specificity. They contain SH3-binding motifs as well as F-actin binding motifs, thus they are generally believed to play a role in the regulation of cytoskeletal rearrangements. In accordance with their proposed rule, proteins like ADF, cofilin and LIMK1 are slingshot substrates.
Three PRL genes were described in mammals (PRL-1, PRL-2 and PRL-3). They share a high sequence identity and possess an N-terminal prenylation sequence (CAAX box). Despite their up-regulation in colorectal cancer, the role and substrate specificity of PRLs is poorly known.
The four mammalian Cdc14 proteins (named KAP, Cdc14A, Cdc14B and PTP9Q22) play a crucial role in cell cycle regulation by dephosphorylating cyclin-dependent kinases, most importantly CDK2.
There are five PTEN-like phosphatases encoded in the human genome. Though structurally related to other DUSPs, these are not strictly phosphorotein-phosphatases, since their most important substrates are phosphorylated inositol lipids. Myotubularins similarly display a preference towards certain phosphatidyl inositols.
MKPs form a rather large family, with some 11 well-characterized members. They are responsible for the dephosphorylation of active mitogen-activated protein kinases (MAPKs). In accordance with this role, several (but not all) MKPs contain an additional, N-terminal domain. Although structurally similar to Cdc14, this extra domain is inactive, and plays a role in substrate recruitment. The surface of this substrate-binding domain mimics the D-motifs found in intrinsically disordered substrates of MAPKs.


3-deoxyoctulosonase

In enzymology, a 3-deoxyoctulosonase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 3-deoxyoctulosonyl-lipopolysaccharide and H2O, whereas its two products are 3-deoxyoctulosonic acid and lipopolysaccharide.
This enzyme belongs to the family of hydrolases, specifically those glycosidases that hydrolyse O- and S-glycosyl compounds. The systematic name of this enzyme class is 3-deoxyoctulosonyl-lipopolysaccharide hydrolase. This enzyme is also called alpha-Kdo-ase.


Pikachurin

Pikachurin, also known as AGRINL (AGRINL) and EGF-like, fibronectin type-III and laminin G-like domain-containing protein (EGFLAM), is a protein that in humans is encoded by the "EGFLAM" gene.
Pikachurin is a dystroglycan-interacting protein which has an essential role in the precise interactions between the photoreceptor ribbon synapse and the bipolar dendrites. The binding with dystroglycan (DG) depends on several factors (glycosylation of DG, presence of divalent cations, presence of other proteins).
A non-correct binding between pikachurin and DG is associated with muscular dystrophies that often involve eye abnormalities.
Discovery and nomenclature.
Pikachurin is an extracellular matrix-like retinal protein first discovered in 2008 in Japan by Shigeru Sato et al. and named after Pikachu, a species of the "Pokémon" franchise. The name of this "nimble" protein was inspired by Pikachu's "lightning-fast moves and shocking electric effects".
Pikachurin was initially identified in a microarray analysis of gene expression profiles of the retinas of wild-type and Otx2 knockout mice. A RT-PCR analysis was used to confirm that Otx2 regulates the expression of pikachurin, it was known because there was an absence of expression of pikachurin in the Otx2 mice retina, so it indicates that Otx2 regulates pikachurin. The localization of pikachurin to synaptic cleft in the photoreceptor ribbon synapse was determined using fluorescent antibodies. Tissue targeting of gene disruption of pikachurin was used to determine that this protein is necessary for proper synaptic signal transmission and visual function. α-dystroglycan was shown to interact with pikachurin through immunoprecipitation.
Pikachurin-dystroglycan interaction.
Dystroglycan ligand with other proteins is essential. Glycosylation of dystroglycan is necessary for its ligand binding activity. Mutations in glycosyltransferase enzymes cause abnormal glycosylation of dystroglycan. This hypoglycosylation is associated with less binding with other proteins and causes some congenital muscular dystrophy. Pikachurin is the most recently identified dystroglycan ligand protein and is localized in the synaptic cleft in the photoreceptor ribbon synapse. The binding between dystroglycan and pikachurin requires divalent cations. Ca2+ produces strongest binding; Mn2+ produces only faint bindings and no binding with Mg2+ alone. Dystroglycan has different domains that allow multiple Ca2+ sites to form a stable pikachurin-dystroglycan connection. This shows that pikachurin can form oligomeric structures; and suggests the possibility of clustering effects can be important in modulating pikachurin-dystroglycan interactions.
Another thing to be considered is that the presence of NaCl (0.5M) strongly inhibits interaction between DG and other ligand proteins but has a modest inhibitory effect with pikachurin-DG ligand. This shows that there are differences between the binding of pikachurin-DG binding and DG binding with other proteins.
Pikachurin seems to have more domains to bind with DG than other proteins. For example, experiments in ligand competition shows that presence of pikachurin inhibits laminin-111 binding with DG, but high concentrations of laminin-111 do not inhibit pikachurin binding to DG.
Function.
The protein is colocalized with both dystrophin and dystroglycan at the ribbon synapses.
Pikachurin, along with laminin, perlecan, agrin, neurexin, binds to α-dystroglycan in the extracellular space. As such, pikachurin, as well as the other previously-mentioned proteins, is necessary for the proper functioning of dystroglycan. Pikachurin is necessary for the apposition of presynaptic and postsynaptic termini in the ribbon synapse; deletion of pikachurin causes an abnormal electroretinogram, similarly to the deletion of nestin.
Ribbon synapse relation.
Synapse formation is crucial for the mammalian CNS (central nervous system) to function correctly. Retinal photoreceptors finish at the axon terminal which forms a specialized structure, the ribbon synapse, which specifically connects photoreceptor synaptic terminals with bipolar and horizontal cell terminals in the outer plexiform layer (OPL) of the retina.
It is clear that Pikachurin, an extracellular matrix–like retinal protein, is localized to the synaptic cleft in the photoreceptor ribbon synapse. It is demonstrated that with a lack of Pikachurin, there is an improper apposition of the bipolar cell dendritic tips to the photoreceptor ribbon synapses, resulting in alterations in synaptic signal transmission and visual function. The function of Pikachurin remains unknown, but it is a fact that pikachurin is critically involved in the normal photoreceptor ribbon synapse formation and also in physiological functions of visual perception.
Associated pathologies: muscular dystrophies.
Congenital muscular dystrophies (CMD) such as muscle-eye-brain disease are caused by defective glycosylation of α-dystroglycan (α-DG) exhibit defective photoreceptor synaptic function. Pikachurin plays an essential role in CMD. Precise interactions between the photoreceptor ribbon synapse and the bipolar dendrites which are realized due to Pikachurin may advance our understanding of the molecular mechanisms underlying the retinal electrophysiological abnormalities observed in muscular dystrophy patients. The muscle-eye-brain dystrophy is caused by mutations in POMGnT1 or LARGE. These two genes mediated a post-translational modification on O-mannose, which is essential for pikachurin binding to dystroglycan, so people who suffer muscle-eye-disease have an hypoglycosylation of pikachurin-α-dystroglycan interactions.
Therapeutic applications.
Since pikachurin seems to provide better visual acuity, Sato et al. of the Osaka Bioscience Institute believe that the protein could be used to develop a treatment for retinitis pigmentosa and other eye disorders.


Alanopine dehydrogenase

Alanopine dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 2 substrates of this enzyme are 2,2'-iminodipropanoate, and nicotinamide adenine dinucleotide+. water is excluded since water is 55M and does not change. Its 4 products are L-alanine, pyruvate, nicotinamide adenine dinucleotide, and hydrogen ion.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 2,2'-iminodipropanoate:NAD+ oxidoreductase (L-alanine-forming). Other names in common use include ALPDH, alanopine[meso-N-(1-carboxyethyl)-alanine]dehydrogenase, meso-N-(1-carboxyethyl)-alanine:NAD+ oxidoreductase, alanopine: NAD+ oxidoreductase, ADH, and alanopine:NAD+ oxidoreductase.


All-trans-nonaprenyl diphosphate synthase

All-trans-nonaprenyl diphosphate synthase (previously known as "trans"-octaprenyl"trans"transferase) may refer to:


LRRC57

Leucine rich repeat containing 57, also known as LRRC57, is a protein that in humans is encoded by the "LRRC57" gene.
Function.
The exact function of LRRC57 is not known. It is a member of the leucine-rich repeat family of proteins, which are known to be involved in protein-protein interactions.
Protein sequence.
As is customary for leucine-rich repeat proteins, the sequence is shown below with the repeats starting on their own lines. The beginning of each repeat is a β-strand, which forms a β-sheet along the concave side of the protein. The convex side of the protein is formed by the latter half of each repeat, and may consist of a variety of structures, including α-helices, 310 helices, β-turns, and even short β-strands.
Note that the 5' and 3' UTR both are rich in leucines, suggesting that they may be degenerate repeats (the overall protein is 19.7% leucine and 7.5% asparagine, both very rich).
The following layout of the LRRC57 amino acid sequence makes it easy to discern the LxxLxLxxNxxL consensus sequence of LRRs.
Homology.
LRRC57 is exceedingly well conserved, as shown by the following multiple sequence alignment, prepared using ClustalX2. The cyan and yellow highlights call out regions of high conservation and the repeats.
The following table provides a few details on orthologs of the human version of LRRC57. To save space, not all of these orthologs are included in the above multiple sequence alignment. These orthologs were gathered from BLAT. and BLAST searches
Gene neighborhood.
The LRRC57 gene has interesting relationships to its neighbors – HAUS2 upstream and SNAP23 downstream, as shown below for human.
Shown below is the neighborhood for the mouse ortholog. Note that the neighbors are the same, which is true for most vertebrates.
Note the close proximity between LRRC57 and HAUS2/CEP27 (the same gene by different names). In humans, the exons are 50bp apart, whereas in mouse, they overlap, as shown in the closeup, below. This close relationship may partially explain the high conservation of LRRC57, as it would require a mutation to be stable in both genes at the same time.
The relationship to the downstream neighbor, SNAP23 is also interesting. Quoting from the AceView entry: "373 bp of this gene are antisense to spliced gene SNAP23, raising the possibility of regulated alternate expression". Taking the reverse complement of the LRRC57 cDNA and aligning it with the SNAP23 cDNA does show high similarity, as shown in this partial alignment:
Predicted post-translational modifications.
The tools on the ExPASy Proteomics site predict the following post-translational modifications:
The predicted modifications for Homo sapiens are shown on the following conceptual translation. The cyan highlights are predicted phosphorylation sites and the yellow highlights are as labeled. The red boxes show predictions that are conserved across all four organisms.
The sites for all four organisms are highlighted on the following multiple sequence alignment.
Note that the phosphorylation at S201 and the sulfation at Y224 are the only well conserved predictions across all four organisms.
Structure.
The structure of LRRC57 is not known. However, a protein BLAST search against the protein databank returns a similar protein (), with an E-value of 3E−14. It is also a leucine rich repeat containing seven repeats of the same length as LRRC57, described as "Eptatretus burgeri" (inshore hagfish) variable lymphocyte receptors A29.


Tetrahydromethanopterin

Tetrahydromethanopterin (THMPT, ) is a coenzyme in methanogenesis. It is the carrier of the C1 group as it is reduced to the methyl level, before transferring to the coenzyme M.
Tetrahydrosarcinapterin (THSPT, ) is a modified form of THMPT, wherein a glutamyl group linked to the 2-hydroxyglutaric acid terminus.
THMPT is the main platform for C1 transformations.
N-Formylmethanofuran donates the C1 group to the N5 site of the pterin to give the formyl- THMPT. The formyl group subsequently condenses intramolecularly to give methenyl- , which is then reduced to methylene- THMPT. Methylene- MPT is subsequently converted, using coenzyme F420 as the electron source, to methyl- THMPT, catalyzed by F420-dependent methylene- THMPT reductase. Methyl- THMPT is the methyl donor to coenzyme M, a conversion mediated by methyl- THMPT:coenzyme M methyl-transferase.
Comparison with tetrahydrofolic acid.
THMPT is related to the better known tetrahydrofolic acid (THFA, ). The most important difference between THMPT and THFA is that THFA has an electron-withdrawing carbonyl group on the phenyl ring. As a consequence, methenyl- THMPT is more difficult to reduce than methenyl- THFA. Reduction is effected by a so-called iron-sulfur cluster free hydrogenase. The cumbersome name distinguishes this hydrogenase from the so-called Fe-only hydrogenases that do contain Fe-S cluster.


3-deoxy-8-phosphooctulonate synthase

In enzymology, a 3-deoxy-8-phosphooctulonate synthase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are phosphoenolpyruvate, D-arabinose 5-phosphate, and H2O, whereas its two products are 2-dehydro-3-deoxy-D-octonate 8-phosphate and phosphate.
This enzyme participates in lipopolysaccharide biosynthesis.
Nomenclature.
This enzyme belongs to the family of transferases, specifically those transferring aryl or alkyl groups other than methyl groups. The systematic name of this enzyme class is phosphoenolpyruvate:D-arabinose-5-phosphate C-(1-carboxyvinyl)transferase (phosphate-hydrolysing, 2-carboxy-2-oxoethyl-forming). Other names in common use include 2-dehydro-3-deoxy-D-octonate-8-phosphate, D-arabinose-5-phosphate-lyase (pyruvate-phosphorylating), 2-dehydro-3-deoxy-phosphooctonate aldolase, 2-keto-3-deoxy-8-phosphooctonic synthetase, 3-deoxy-D-manno-octulosonate-8-phosphate synthase, 3-deoxy-D-mannooctulosonate-8-phosphate synthetase, 3-deoxyoctulosonic 8-phosphate synthetase, KDOP synthase, and phospho-2-keto-3-deoxyoctonate aldolase.


GABA aminotransferase

GABA aminotransferase may refer to:


Aldose-6-phosphate reductase (NADPH)

In enzymology, an aldose-6-phosphate reductase (NADPH) () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are D-sorbitol 6-phosphate and NADP+, whereas its 3 products are D-glucose 6-phosphate, 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 D-aldose-6-phosphate:NADP+ 1-oxidoreductase. Other names in common use include aldose 6-phosphate reductase, NADP+-dependent aldose 6-phosphate reductase, A6PR, aldose-6-P reductase, aldose-6-phosphate reductase, alditol 6-phosphate:NADP+ 1-oxidoreductase, and aldose-6-phosphate reductase (NADPH).


Ketose

A ketose is a monosaccharide containing one ketone group per molecule. The simplest ketose is dihydroxyacetone, which has only three carbon atoms, and it is the only one with no optical activity. All monosaccharide ketoses are reducing sugars, because they can tautomerize into aldoses via an enediol intermediate, and the resulting aldehyde group can be oxidised, for example in the Tollens' test or Benedict's test. Ketoses that are bound into glycosides, for example in the case of the fructose moiety of sucrose, are nonreducing sugars.
Examples of ketoses.
All ketoses listed here are 2-ketoses, in other words, the carbonyl group is on the second carbon atom from the end:
Chemistry.
Ketoses and aldoses can be chemically differentiated through Seliwanoff's test, where the sample is heated with acid and resorcinol. The test relies on the dehydration reaction which occurs more quickly in ketoses, so that while aldoses react slowly, producing a light pink color, ketoses react more quickly and strongly to produce a dark red color. Ketoses can isomerize to aldoses through the Lobry-de Bruyn-van Ekenstein transformation.


Fluoren-9-ol dehydrogenase

In enzymology, a fluoren-9-ol dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are fluoren-9-ol, NAD+, and NADP+, whereas its 4 products are fluoren-9-one, NADH, 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 fluoren-9-ol:NAD(P)+ oxidoreductase. This enzyme participates in fluorene degradation.


Modification methylase

Modification methylase may refer to:


Glycoside hydrolase family 52

In molecular biology, glycoside hydrolase family 52 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 52 CAZY GH_52 comprises enzymes with only one known activity; beta-xylosidase ().
Proteins harboring beta-xylosidase and xylanase activities have been identified in the Gram-positive, facultative thermophilic aerobe "Bacillus stearothermophilus" 21. This microbe, which functions in xylan degradation, can utilise xylan as a sole source of carbon. The enzyme hydrolyses 1,4-beta-D-xylans, removing successive D-xylose residues from the non-reducing termini. It also hydrolyses xylobiose.


Ent-isokaurene C2-hydroxylase

Ent-isokaurene C2-hydroxylase (, "CYP71Z6") is an enzyme with systematic name "ent-isokaurene,NADPH:oxygen oxidoreductase (hydroxylating)". This enzyme catalyses the following chemical reaction
Ent-isokaurene C2-hydroxylase performs the initial step in the conversion of ent-isokaurene to the antibacterial oryzalides in rice, "Oryza sativa".


GDP-6-deoxy-D-talose 4-dehydrogenase

In enzymology, a GDP-6-deoxy-D-talose 4-dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are GDP-6-deoxy-D-talose, NAD+, and NADP+, whereas its 4 products are GDP-4-dehydro-6-deoxy-D-mannose, NADH, 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 GDP-6-deoxy-D-talose:NAD(P)+ 4-oxidoreductase. This enzyme is also called guanosine diphospho-6-deoxy-D-talose dehydrogenase. This enzyme participates in fructose and mannose metabolism.


Xylose

Xylose ("cf." , "xylon", "wood") is a sugar first isolated from wood, and named for it. Xylose is classified as a monosaccharide of the aldopentose type, which means that it contains five carbon atoms and includes an aldehyde functional group. It is derived from hemicellulose, one of the main constituents of biomass. Like most sugars, it can adopt several structures depending on conditions. With its free aldehyde group, it is a reducing sugar.
Structure.
The acyclic form of xylose has chemical formula HOCH2(CH(OH))3CHO. The cyclic hemiacetal isomers are more prevalent in solution and are of two types: the pyranoses, which feature six-membered C5O rings, and the furanoses, which feature five-membered C4O rings (with a pendant CH2OH group). Each of these rings is subject to further isomerism, depending on the relative orientation of the anomeric hydroxy group.
The dextrorotary form, -xylose, is the one that usually occurs endogenously in living things. A levorotary form, -xylose, can be synthesized.
Occurrence.
Xylose is the main building block for the hemicellulose xylan, which comprises about 30% of some plants (birch for example), far less in others (spruce and pine have about 9% xylan). Xylose is otherwise pervasive, being found in the embryos of most edible plants. It was first isolated from wood by Finnish scientist, Koch, in 1881, but first became commercially viable, with a price close to sucrose, in 1930.
Xylose is also the first saccharide added to the serine or threonine in the proteoglycan type O-glycosylation, and, so, it is the first saccharide in biosynthetic pathways of most anionic polysaccharides such as heparan sulfate and chondroitin sulfate.
Xylose is also found in some species of Chrysolinina beetles, including "Chrysolina coerulans", they have cardiac glycosides (including xylose) in their defensive glands.
Applications.
Chemicals.
The acid-catalysed degradation of hemicellulose gives furfural, a precursor to synthetic polymers and to tetrahydrofuran.
Human consumption.
Xylose is metabolised by humans, although it is not a major human nutrient and is largely excreted by the kidneys. Humans can obtain xylose only from their diet. An oxidoreductase pathway is present in eukaryotic microorganisms. Humans have enzymes called protein xylosyltransferases (XYLT1, XYLT2) which transfer xylose from UDP to a serine in the core protein of proteoglycans.
Xylose contains 2.4 calories per gram (lower than glucose or sucrose, approx. 4 calories per gram).
Animal medicine.
In animal medicine, xylose is used to test for malabsorption by administration in water to the patient after fasting. If xylose is detected in blood and/or urine within the next few hours, it has been absorbed by the intestines.
High xylose intake on the order of approximately 100g/kg of animal body weight is relatively well tolerated in pigs, and in a similar manner to results from human studies, a portion of the xylose intake is passed out in urine undigested.
Hydrogen production.
In 2014 a low-temperature , atmospheric-pressure enzyme-driven process to convert xylose into hydrogen with nearly 100% of the theoretical yield was announced. The process employs 13 enzymes, including a novel polyphosphate xylulokinase (XK).
Derivatives.
Reduction of xylose by catalytic hydrogenation produces the sugar substitute xylitol.


Neutral and basic amino acid transport protein rBAT

Neutral and basic amino acid transport protein rBAT is a protein that in humans is encoded by the "SLC3A1" gene.
Mutations in the SLC3A1 gene are associated with cystinuria.


BNR/Asp-box repeat

BNR/Asp-box repeat is a repetitive sequence of amino acids contained in some proteins.
Members of this family contain multiple BNR (bacterial neuraminidase repeat) repeats or Asp-boxes. The repeats are short, however the repeats are never found closer than 40 residues together suggesting that the repeat is structurally longer. These repeats are found in a variety of non-homologous proteins, including bacterial ribonucleases, sulphite oxidases, reelin, netrins, sialidases, neuraminidases, some lipoprotein receptors, and a variety of glycosyl hydrolases.
Members of this family contain multiple BNR (bacterial neuraminidase repeat) repeats or Asp-boxes.
Examples.
Human genes encoding proteins containing this domain include:


(tyrosine 3-monooxygenase) kinase

In enzymology, a [tyrosine 3-monooxygenase] kinase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ATP and tyrosine 3-monooxygenase, whereas its two products are ADP and phospho-(tyrosine-3-monooxygenase).
This enzyme belongs to the family of transferases, specifically those transferring a phosphate group to the sidechain oxygen atom of serine or threonine residues in proteins (protein-serine/threonine kinases). The systematic name of this enzyme class is ATP:[tyrosine-3-monoxygenase] phosphotransferase. Other names in common use include pheochromocytoma tyrosine hydroxylase-associated kinase, STK4, and tyrosine 3-monooxygenase kinase (phosphorylating). This enzyme participates in MAPK signaling pathway and non-small cell lung cancer.


Biochanin-A reductase

In enzymology, a biochanin-A reductase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are dihydrobiochanin A and NADP+, whereas its 3 products are biochanin A, NADPH, 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 dihydrobiochanin-A:NADP+ Delta2-oxidoreductase. This enzyme participates in isoflavonoid biosynthesis.


2-oxobutyrate synthase

In enzymology, a 2-oxobutyrate synthase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are 2-oxobutanoate, CoA, and oxidized ferredoxin, whereas its 3 products are propanoyl-CoA, CO2, and reduced ferredoxin.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with an iron-sulfur protein as acceptor. The systematic name of this enzyme class is 2-oxobutanoate:ferredoxin 2-oxidoreductase (CoA-propanoylating). Other names in common use include alpha-ketobutyrate-ferredoxin oxidoreductase, 2-ketobutyrate synthase, alpha-ketobutyrate synthase, 2-oxobutyrate-ferredoxin oxidoreductase, and 2-oxobutanoate:ferredoxin 2-oxidoreductase (CoA-propionylating). This enzyme participates in propanoate metabolism.


Dihydroceramide desaturase

Dihydroceramide desaturase is the enzyme involved in the conversion of dihydroceramide into ceramide by inserting the 4,5-"trans"-double bond to the sphingolipid backbone of dihydroceramide. DDase require the and the NAD(P)H as cofactor.
The activity of DDase is influenced by several factors as
N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11), is the inhibitor DDase activity.


C3 convertase

The term C3 convertase may refer to:


Dihydroorotate dehydrogenase (fumarate)

Dihydroorotate dehydrogenase (fumarate) (, "dihydroorotate oxidase, pyr4 (gene)") is an enzyme with systematic name "(S)-dihydroorotate:fumarate oxidoreductase". This enzyme catalyses the following chemical reaction
This enzyme contains FMN.


Carboxypeptidase A inhibitor

In molecular biology, the carboxypeptidase A inhibitor family is a family of proteins which is represented by the well-characterised metallocarboxypeptidase A inhibitor (MCPI) from potatoes, which belongs to the MEROPS inhibitor family I37, clan IE. It inhibits metallopeptidases belonging to MEROPS peptidase family M14, carboxypeptidase A. In Russet Burbank potatoes, it is a mixture of approximately equal amounts of two polypeptide chains containing 38 or 39 amino acid residues. The chains differ in their amino terminal sequence only and are resistant to fragmentation by proteases. The structure of the complex between bovine carboxypeptidase A and the 39-amino-acid carboxypeptidase A inhibitor from potatoes has been determined at 2.5-Angstrom resolution.
The potato inhibitor is synthesised as a precursor, having a 29 amino acid N-terminal signal peptide, a 27 amino acid pro-peptide, the 39 amino acid mature inhibitor region and a 7 amino acid C-terminal extension. The 7 amino acid C-terminal extension is involved in inhibitor inactivation and may be required for targeting to the vacuole where the mature active inhibitor accumulates.
The N-terminal region and the mature inhibitor are weakly related to other solananaceous proteins found in this family, from potato, tomato and henbane, which have been incorrectly described as metallocarboxypeptidase inhibitors.


Anthranilic hydroxylase

Anthranilic hydroxylase may refer to:


D-arabitol-phosphate dehydrogenase

D-arabitol-phosphate dehydrogenase (, "APDH", "D-arabitol 1-phosphate dehydrogenase", "D-arabitol 5-phosphate dehydrogenase") is an enzyme with systematic name "D-arabitol-phosphate:NAD+ oxidoreductase". This enzyme catalyses the following chemical reaction
This enzyme participates in arabitol catabolism. The enzyme also converts D-arabitol 5-phosphate to D-ribulose 5-phosphate at a lower rate.


Beta-propeller phytase

β-propeller phytases (BPPs) are a group of enzymes (i.e. protein superfamily) with a round beta-propeller structure. BPPs are phytases, which means that they are able to remove (hydrolyze) phosphate groups from phytic acid and its phytate salts. Hydrolysis happens stepwise and usually ends in "myo"-inositol triphosphate product which has three phosphate groups still bound to it. The actual substrate of BPPs is calcium phytate and in order to hydrolyze it, BPPs must have Ca2+ ions bound to themselves. BPPs are the most widely found phytase superfamily in the environment and they are thought to have a major role in phytate-phosphorus cycling in soil and water. As their alternative name alkaline phytase suggests, BPPs work best in basic (or neutral) environment. Their pH optima is 6–9, which is unique among the phytases.
Potential uses.
As of April 2018, BPPs are not used commercially, but they may have potential for such use. Histidine acid phytases (HAPs) are the only group of phytases which are used in animal feed at the moment.
Animal feed.
Recombinant phytases are added commonly in agriculture to animal feed of monogastric animals to enhance the feed's nutrient bioavailability. These nutrients include phosphorus which is bound to phytates in the form of their phosphate groups. In contrast to ruminants like cattle, gut bacteria of monogastric animals like pigs and chickens can't properly hydrolyze these groups free so that the digestive system of the animal can use the phosphorus. Unabsorbed phosphorus is thus wasted and may end up into the environment in animal manure via agricultural runoff and cause eutrophication. Phytic acid can also work as an antinutrient: it can chelate calcium from feed and decrease its bioavailability up to 60–70% of the feed's total calcium content. Phytase addition improves calcium availability and can also improve the bioavailability of iron and zinc. It might also increase the availability of copper and manganese. Amino acid bioavailability is not enhanced significantly.
In comparison to histidine acid phytases (HAPs), which are often unstable in temperatures higher than 65 °C, BPPs can naturally withstand high temperatures of 80–85 °C. Such temperatures are commonly used in pelleting of animal feed during its manufacture. Unlike HAPs, BPPs have a neutral or alkaline pH optima, which makes it possible to use them in neutral or alkaline environments. This expands potential applications for phytases. BPPs could be used in aquatic animal feed because many of these animals like fishes and shrimps have a neutral or alkaline gastrointestinal tract. BPPs are also phytate specific unlike HAPs, which hydrolyze also other phosphate containing molecules like ADP, GTP and NADH. However, BPPs are catalytically more than 2–60 times slower than current the HAPs. HAPs have a specific catalytic activity of 100–3000 U mg−1. BPPs usually have a specific catalytic activity of less than 50 U mg−1. Because of such low activity practical use of BPPs requires much more research.
Structure.
As of April 2018, 7 BPP crystal structures were known: 3AMR, 3AMS, 1H6L, 1POO, 2POO, 1CVM and 1QLG.
Masses of known BPPs are approximately 35–68 kDa. Their donut-shaped β-propeller structure consists of 6 antiparallel beta sheet structures or "blades". One of these blades has 5 β-sheets (blade number 5 in the picture in the beginning of this article) and the rest have 4 β-sheets. There are hydrophobic interactions between these blades which are thought to keep the propeller structure together. These blades form a tunnel-like hole through the enzyme. This tunnel binds some water molecules. In front of the tunnel is the enzyme's active site which is positively charged in total due to Ca2+ ions it binds and certain positive amino acid residues. This site binds negatively charged calcium phytate and hydrolyzes phosphates from it.
Motifs.
A 2008 study by Huang et al. compared 66 BPP peptide sequences and found that sequence motifs DA[A/T/E]DDPA[I/L/V]W and NN[V/I]D[I/L/V]R[Y/D/Q] were conserved in all of the studied BPPs. R[Y/D/Q] for example signifies that R and Y, D or Q were found in the sequence, i.e. RY or RD or RQ. 2014 study by Kumar et al. compared 44 BPPs and found 10 motifs. Two of these, DDPAIW[VI][HN]PK[DN]P[ESA]KS and NN[F/V]D[I/V/L], were found in all of the studied BPPs. These were noted to be similar to the ones found in the 2008 study by Huang et al.
Calcium dependence and inhibitors.
BPPs are calcium dependent metalloproteins. Their active site has a number of calcium cations (Ca2+) bound to it via negatively charged amino acid carboxylate groups. Positive calcium ions are needed to make binding of the negative phytate electrically favorable. Binding happens via phytate's negatively charged phosphate groups along with certain positive amino acid residues of the BPP which bind directly to the phytate. Ca2+ concentrations also have an effect on BPP pH optima and thermostability: e.g. with "Bacillus sp". KHU-10 BPP the activity is highest with 10 mM of added CaCl2 at 60 °C and pH 6–9.5. Without added CaCl2 the pH highest activity is at 40 °C and pH 6.5–8.5.
Removal of Ca2+ leads to the loss of catalytic activity which is why Ca2+ chelating EDTA inhibits BPPs. Certain point mutations of the calcium binding amino acids also stops enzyme function. Divalent ions like Cd2+, Mn2+, Cu2+, Ba2+, Hg2+, Zn2+, Co2+ and Fe2+ inhibit BPPs by replacing Ca2+ within the enzyme. This is probably due to the fact that these cations are too small in comparison to Ca2+ ions, which have a Van der Waals radius (WDV) of 0.99 Å. Co2+ has VDW of 0.74 Å for example and is thus probably too small to carry out the same tasks that Ca2+ can. However, Sr2+ ions can replace Ca2+ at least in certain cases without total loss of catalytic function. Sr2+ VDW radius is 1.12 Å, and is similar to that of Ca2+. Similar compatibility between different ions can be seen in some other enzymes, too.
High Ca2+ concentration can enhance BPP catalysis rate up to a limit. When Ca2+ concentration surpasses this limit, extra Ca2+ ions begin to work as competitive inhibitors. High concentrations of free phytate which not bound to Ca2+ also inhibits BPPs. This happens possibly via free phytate mediated chelation of the Ca2+ bound to BPPs.
Other types of inhibitors include oxyanionic (oxygen binding) molybdate, tungstate and vanadate. It has been suggested that inhibition with these oxyanions happens because they form trigonal bipyramidal complexes within the active site of the enzyme which are similar to the transition state of the phytate's phosphate group during its hydrolysis. Orthophosphate which is released from phytic acid works as a competitive inhibitor of BPPs. Phytic acid analogue "myo"-inositol-hexasulphate (IHS) inhibits BPPs and this has been used as an aid in BPP structural studies due to its similarity with phytic acid (see 3AMR).
Hydrolysis mechanism.
In a hydrolysis mechanism suggested in 2001 by Shin et al. the Ca2+ ions bound to the BPP are divided to "hydrolysis" and "affinity site" ions. In the hydrolysis site, Ca2+ help the phosphate about to be removed bind to the active site. They also activate a water molecule that participates in the hydrolysis by turning it in to an OH− ion and stabilize the transition state during catalysis. Affinity area ions increase phytate affinity to the active site and keep the phytate still during hydrolysis from its other phosphate groups. Hydrolysis is repeated stepwise until a "myo"-inositol product with three phosphates is obtained. Other studies support product with three phosphates, but more phosphates can be removed under extreme conditions such as high BPP concentration and lengthened incubation time.
Actual hydrolysis suggested by Shin et al. happens in two steps. Second one is slower and limits the total reaction speed. In the first step carbonyl group withdraws electrons from phosphorus of the phosphate making it electron poor, i.e. leaving it with a positive charge. Simultaneously OH− donates an electron pair to the nominally positive phosphorus in phosphate. A trigonal bipyramidal intermediate state is formed. In the second step phosphoester bond is cleaved when an acidic amino acid residue (BH+) donates a proton to the oxygen in the bond. Phosphate group is thus cleaved off.
Hydrolysis routes.
Multiple suggested hydrolysis routes exists, but it is uncertain which one is correct or if multiple routes exist. These hydrolysis routes are summarized below.


N-acetylglucosaminyltransferase I

N-acetylglucosaminyltransferase I may refer to:


Berberine reductase

Berberine reductase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are (R)-canadine and nicotinamide adenine dinucleotide phosphate ion, whereas its 3 products are berberine, nicotinamide adenine dinucleotide phosphate, and hydrogen ion.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is (R)-tetrahydroberberine:NADP+ oxidoreductase. This enzyme is also called (R)-canadine synthase.


EP300

Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the "EP300" gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.
The EP300 gene is located on the long (q) arm of the human chromosome 22 at position 13.2. This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein.
EP300 is closely related to another gene, CREB binding protein, which is found on human chromosome 16.
Function.
p300 HAT functions as histone acetyltransferase that regulates transcription via chromatin remodeling, and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein.
p300 HAT contains a bromodomain which is involved in IL6 signaling.
This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and, thus, plays a role in the stimulation of hypoxia-induced genes such as VEGF.
Mechanism.
The p300 protein carries out its function of activating transcription by binding to transcription factors, and the transcription machinery. On the basis of this function, p300 is called a transcriptional coactivator. The p300 interaction with transcription factors is managed by one or more of p300 domains: the nuclear receptor interaction domain (RID), the KIX domain (CREB and MYB interaction domain), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). The last four domains, KIX, TAZ1, TAZ2 and IBiD of p300, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53.
Clinical significance.
Mutations in the EP300 gene are responsible for a small percentage of cases of Rubinstein-Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein-Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.
Chromosomal rearrangements involving chromosome 22 have rarely been associated with certain types of cancer. These rearrangements, called translocations, disrupt the region of chromosome 22 that contains the EP300 gene. For example, researchers have found a translocation between chromosomes 8 and 22 in several people with a cancer of blood cells called acute myeloid leukemia (AML). Another translocation, involving chromosomes 11 and 22, has been found in a small number of people who have undergone cancer treatment. This chromosomal change is associated with the development of AML following chemotherapy for other forms of cancer.
Mutations in the EP300 gene have been identified in several other types of cancer. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. Somatic mutations in the EP300 gene have been found in a small number of solid tumors, including cancers of the colon and rectum, stomach, breast, and pancreas. Studies suggest that EP300 mutations may also play a role in the development of some prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. In cancer cells, EP300 mutations prevent the gene from producing any functional protein. Without p300, cells cannot effectively restrain growth and division, which can allow cancerous tumors to form.
Interactions.
EP300 has been shown to interact with:


3-deoxy-D-manno-oct-2-ulosonic acid transferase

3-deoxy-D-manno-oct-2-ulosonic acid transferase may refer to:


Tetrose

A tetrose is a monosaccharide with 4 carbon atoms. They have either an aldehyde functional group in position 1 (aldotetroses) or a ketone functional group in position 2 (ketotetroses).
The aldotetroses have two chiral centers (asymmetric carbon atoms) and so 4 different stereoisomers are possible. There are two naturally occurring stereoisomers, the enantiomers of erythrose and threose having the but not the enantiomers. The ketotetroses have one chiral center and, therefore, two possible stereoisomers: erythrulose (- and -form). Again, only the enantiomer is naturally occurring.
Biological Functions.
There are a few known ways that tetrose sugars are used in nature. Some are seen in metabolic pathways and others are known to affect certain enzymes.
Intermediates in the Pentose Phosphate Pathway.
One of the metabolic pathways that a tetrose is involved in is the Pentose Phosphate Pathway. In the Pentose Phosphate Pathway, there is an oxidative stage and a non-oxidative stage. A tetrose sugar, D-erythrose, is utilized in the non-oxidative stage, where D-ribulose 5-phosphate is generated into a 6 carbon sugar (fructose 6-phosphate) and a 3 carbon sugar (glyceraldehyde 3-phosphate). Both of these molecules can be used elsewhere in the body.
D-erythrose 4-phosphate is generated as a product of a reaction called transaldolation. In the Pentose Phosphate Pathway, a transaldolase removes the first 3 carbon molecules of sedoheptulose 7-phosphate and places them onto a glyceraldehyde 3-phosphate. The transaldolase utilizes a Schiff base to perform a reverse aldol reaction and a forward aldol reaction in its mechanism, generating an erythrose 4-phosphate and fructose 6-phosphate. The erythrose 4-phosphate is an important intermediate in the Pentose Phosphate Pathway because it is then used in the final non-oxidative step of the pathway.
The final non-oxidative step of the pathway is a transketolase reaction. A transketolase utilizes a thiamine pyrophosphate, or TPP cofactor, to break the unfavorable bond between the carbon in a carbonyl and the alpha carbon. TPP attacks a xylulose 5-phosphate molecule and facilitates the cleavage of the bond between the C2 (carbonyl carbon) and the C3 (alpha carbon), where glyceraldehyde 3-phosphate is released. Then, C2 can attack erythrose 4-phosphate, which forms fructose 6-phosphate. Both of the products of this reaction can enter the gluconeogenesis pathway to regenerate glucose.
Inhibitors of Enzymes.
A tetrose diphosphate molecule, D-threose 2,4-diphosphate, was discovered to be an inhibitor of glyceraldehyde 3-phosphate dehydrogenase. Glyceraldehyde 3-phosphate dehydrogenase is the sixth enzyme used in the glycolysis pathway, and its function is to convert glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate. This tetrose diphosphate molecule inhibits the G3P dehydrogenase from performing catalysis because it oxidizes the enzyme by binding to it at the active site. When tetrose diphosphate is bound to the enzyme, the active site of the enzyme is blocked; therefore phosphorolysis of G3P is unable to occur. High concentrations of tetrose diphosphate must be used to outcompete the substrate, G3P, and block the function of G3P dehydrogenase. With the function of glyceraldehyde 3-phosphate dehydrogenase lost, glycolysis cannot proceed.
D-erythrose 4-phosphate was found to be an inhibitor of phosphoglucose isomerase. Phosphoglucose isomerase is the second enzyme in the glycolysis pathway, and its role is to convert glucose 6-phosphate into fructose 6-phosphate.
In both of these cases, the tetrose is an inhibitor of an enzyme in the glycolysis pathway, preventing it from proceeding onward.


Potassium-dependent sodium-calcium exchanger

Potassium-dependent sodium-calcium exchanger also known as solute carrier family 24 (SLC24) is a type of sodium-calcium exchanger that requires potassium to function.
Family members.
Human genes that encode members of the potassium-dependent sodium-calcium exchanger family include:


Lichesterol

Lichesterol is a sterol made by certain fungi and lichens.


Glycoside hydrolase family 24

In molecular biology, glycoside hydrolase family 24 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 24 CAZY GH_24 comprises enzymes with only one known activity; lysozyme (). This family includes lambda phage lysozyme and "Escherichia coli" T4 phage endolysin. Lysozyme helps to release mature phage particles from the cell wall by breaking down the peptidoglycan. The enzyme hydrolyses the 1,4-beta linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of prokaryotic cell walls. "E. coli" endolysin also functions in bacterial cell lysis and acts as a transglycosylase. The T4 lysozyme structure contains 2 domains, the interface between which forms the active-site cleft. The N-terminus of the 2 domains undergoes a 'hinge-bending' motion about an axis passing through the molecular waist. This mobility is thought to be important in allowing access of substrates to the enzyme active site.


Translocated actin-recruiting phosphoprotein

The translocated actin-recruiting phosphoprotein (Tarp) is a protein that may mediate the invasion of epithelial cells by "Chlamydia trachomatis" using a type three secretion system.


Nicofuranose

Nicofuranose is a niacin derivative used as a hypolipidemic agent.


Pax genes

In evolutionary developmental biology, Paired box (Pax) genes are a family of genes coding for tissue specific transcription factors containing an N-terminal paired domain and usually a partial, or in the case of four family members (PAX3, PAX4, PAX6 and PAX7), a complete homeodomain to the C-terminus. An octapeptide as well as a Pro-Ser-Thr-rich C terminus may also be present. Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.
The paired domain was initially described in 1987 as the "paired box" in the "Drosophila" protein paired (prd; ).
Groups.
Within the mammalian family, there are four well defined groups of Pax genes.
Two more families, Pox-neuro and Pax-α/β, exist in basal bilaterian species. Orthologous genes exist throughout the Metazoa, including extensive study of the ectopic expression in Drosophila using murine Pax6. The two rounds of whole-genome duplications in vertebrate evolution is responsible for the creation of as many as 4 paralogs for each Pax protein.


Oxprenoic acid

Oxprenoic acid, or oxprenoate, is a synthetic steroidal antimineralocorticoid which was never marketed.


Dinoflagellate luciferase

Dinoflagellate luciferase (, "Gonyaulax luciferase") is a specific luciferase, an enzyme with systematic name "dinoflagellate-luciferin:oxygen 132-oxidoreductase". This enzyme catalyses the following chemical reaction
"Dinoflagellate" luciferase is a single protein with three luciferase domains.


Homocysteine methylase

Homocysteine methylase may refer to:


DOCK (protein)

DOCK (Dedicator of cytokinesis) is a family of related proteins involved in intracellular signalling networks. DOCK family members contain a RhoGEF domain to function as guanine nucleotide exchange factors to promote GDP release and GTP binding to specific Small GTPases of the Rho family (e.g., Rac and Cdc42), leading to their activation since Rho proteins are inactive when bound to GDP but active when bound to GTP.
DOCK family proteins are categorised into four subfamilies based on their sequence homology:


Treprostinil

Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Treprostinil is a synthetic analog of prostacyclin (PGI2).
Treprostinil was approved for use in the United States in May 2002.
Medical uses.
Treprostinil is indicated for the treatment of pulmonary arterial hypertension in patients with NYHA Class II-IV symptoms to diminish symptoms associated with exercise. It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route, or in whom these risks are considered warranted. This medication is also available in inhaled and tablet forms.
In patients with pulmonary arterial hypertension requiring transition from epoprostenol sodium (Flolan), treprostinil is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition.
Treprostinil therapy may be effective in treating Degos disease.
Adverse effects.
Common side effects depending on route of administration:
Warnings:
Pharmacology.
Mechanism of action.
The major effects of treprostinil are vasodilation of arteries in the lungs and body. Treprostinil also inhibits platelet aggregation and smooth muscle proliferation.
Pharmacokinetics.
The pharmacokinetics of continuous subcutaneous treprostinil are linear over the dose range of 1.25 to 125 ng/kg/min (corresponding to plasma concentrations of about 15 pg/mL to 18,250 pg/m) and can be described by a two-compartment model. Dose proportionality at infusion rates greater than 125 ng/kg/min has not been studied.
Treprostinil is substantially metabolized by the liver, but the involved enzymes are not currently known. Five metabolites (HU1 through HU5) have been described thus far. Based on the results of in vitro human hepatic cytochrome P450 studies, Remodulin does not inhibit CYP-1A2, 2C9, 2C19, 2D6, 2E1, or 3A. Whether Remodulin induces these enzymes has not been studied.
Dosage and administration.
For infusion.
Treprostinil may be administered as a continuous subcutaneous infusion or continuous intravenous infusion via a small infusion pump that the patient must wear at all times. Treprostinil can be given subcutaneously by continuous infusion using an infusion set connected to an infusion pump, but also may be given intravenously via a central venous catheter if the patient is unable to tolerate subcutaneous administration because of severe site pain or reaction.
Remodulin is supplied in 20 mL vials, containing treprostinil in concentrations of 1 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL. Treprostinil can be administered subcutaneously as supplied. It must be diluted for intravenous infusion with either sterile water or a 0.9% sodium chloride solution prior to administration.
The infusion rate is normally initiated at 1.25 ng/kg/min for new patients, but may be reduced to 0.625 ng/kg/min if the normal rate provokes unwanted side effects in the patient. The infusion rate of treprostinil should be increased no more than 1.25 ng/kg/min per week for the first month, then 2.5 ng/kg/min per week for the remaining duration of infusion. The infusion rate should ideally be high enough to improve symptoms of pulmonary hypertension, while minimizing unpleasant side effects (headache, nausea, emesis, restlessness, anxiety and infusion site pain or reaction). Dosage adjustments may be undertaken more often if tolerated. There is little experience with doses >40 ng/kg/min. Abrupt cessation of infusion should be avoided. Restarting a Remodulin infusion within a few hours after an interruption can be done using the same dose rate. Interruptions for longer periods may require the dose of Remodulin to be re-titrated.
In patients with mild or moderate liver dysfunction, the initial dose of Remodulin should be decreased to 0.625 ng/kg/min ideal body weight and should be increased cautiously. Remodulin has not been studied in patients with severe liver dysfunction.
No studies have been performed in patients with kidney dysfunction. No specific advice about dosing in patients with renal impairment can be given.
Inhaled form.
The inhaled form of treprostinil was approved by the FDA in July 2009 and is marketed as the trade name Tyvaso. The inhaled form is used with a proprietary inhalation device supplied by the manufacturer. Patients use one ampule with inhalation solution a day, four times a day at least four hours apart.
Oral form.
The oral form of treprostinil was approved by the FDA in December 2013 and is marketed as the trade name Orenitram. Orenitram is taken 2 or 3 times daily with food.
History.
During the 1960s a U.K. research team, headed by Professor John Vane began to explore the role of prostaglandins in anaphylaxis and respiratory diseases. Working with a team from the Royal College of Surgeons, Vane discovered that aspirin and other oral anti-inflammatory drugs worked by inhibiting the synthesis of prostaglandins. This finding opened the door to a broader understanding of the role of prostaglandins in the body.
Vane and a team from the Wellcome Foundation had identified a lipid mediator they called “PG-X,” which inhibited platelet aggregation. PG-X, which later would become known as prostacyclin, was 30 times more potent than any other known anti-aggregatory agent.
By 1976, Vane and fellow researcher Salvador Moncada published the first paper on prostacyclin, in the scientific journal "Nature". The collaboration produced a synthetic molecule which was given the name epoprostenol. But like native prostacyclin, the structure of the epoprostenol molecule proved to be unstable in solution, prone to rapid degradation. This presented a challenge for both "in vitro" experiments and clinical applications. To overcome this challenge, the research team that discovered prostacyclin was determined to continue the research in an attempt to build upon the success they had seen with the prototype molecule. The research team synthesized nearly 1,000 analogs.
Remodulin was approved for use in the United States in May 2002, and again in July 2018. Tyvaso, the inhaled form of treprostinil, was approved for use in the United States in July 2009. Orenitram was approved in December 2013.
Trepulmix was approved for use in the European Union in April 2020.
Effect on PPARs.
Treprostinil has demonstrated an effect on PPAR-γ, a transcription factor important in vascular pathogenesis as a mediator of proliferation, inflammation and apoptosis. Through a complementary, yet cyclic AMP-independent pathway, treprostinil activates PPARs, another mechanism that contributes to the anti-growth benefits of the prostacyclin class.


Taspine

Taspine is an alkaloid which acts as a potent acetylcholinesterase inhibitor and cicatrizant. It is found in various plants including "Magnolia x soulangeana" and "Croton lechleri".
The first total synthesis was reported by T. Ross Kelly and Roger L. Xie in 1998.


(S)-2-haloacid dehalogenase

In enzymology, a (S)-2-haloacid dehalogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are (S)-2-haloacid and HO, whereas its two products are (R)-2-hydroxyacid and halide.
This enzyme belongs to the family of hydrolases, specifically those acting on halide bonds in carbon-halide compounds. The systematic name of this enzyme class is (S)-2-haloacid halidohydrolase. Other names in common use include 2-haloacid dehalogenase[ambiguous], 2-haloacid halidohydrolase [ambiguous][ambiguous], 2-haloalkanoic acid dehalogenase, 2-haloalkanoid acid halidohydrolase, 2-halocarboxylic acid dehalogenase II, DL-2-haloacid dehalogenase[ambiguous], L-2-haloacid dehalogenase, and L-DEX. This enzyme participates in gamma-hexachlorocyclohexane degradation and 1,2-dichloroethane degradation.
Structural studies.
As of late 2007, 10 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , , and .


Ectatomin

Ectatomin is a protein toxin from the venom of the ant "Ectatomma tuberculatum". Ectatomin can efficiently insert into the plasma membrane, where it can form channels. Ectatomin was shown to inhibit L-type calcium currents in isolated rat cardiac myocytes. In these cells, ectatomin induces a gradual, irreversible increase in ion leakage across the membrane, which can lead to cell death.
Ectatomin is composed of two subunits, A and B, which are homologous. The structure of ectatomin reveals that each subunit consists of two alpha helices with a connecting hinge region, which form a hairpin structure that is stabilized by disulfide bridges. A disulfide bridge between the hinge regions of the two subunits links the heterodimer together, forming a closed bundle of four alpha helices with a left-handed twist.


Lysine exporter

Lysine Exporters are a superfamily of transmembrane proteins which export amino acids, lipids and heavy metal ions. They provide ionic homeostasis, play a role in cell envelope assembly, and protect from excessive concentrations of heavy metals in cytoplasm. The superfamily was named based on the early discovery of the LysE carrier protein of Corynebacterium glutamicum.
Families.
2.A.75 - The L-Lysine Exporter (LysE) Family
2.A.76 - The Resistance to Homoserine/Threonine (RhtB) Family
2.A.77 - The Cadmium Resistance (CadD) Family
2.A.95 - The 6TMS Neutral Amino Acid Transporter (NAAT) Family
2.A.106 -
2.A.107 - The Mn2+ exporter (MntP) Family
2.A.108 - The Iron/Lead Transporter (ILT) Family
2.A.109 - The Tellurium Ion Resistance (TerC) Family
2.A.113 - The Nickel/Cobalt Transporter (NicO) Family
2.A.116 - The Peptidoglycolipid Addressing Protein (GAP) Family
5.A.1 - The Disulfide Bond Oxidoreductase D (DsbD) Family
The LysE family.
Two members of the LysE family (LysE of "Corynebacterium glutamicum" (TC# 2.A.75.1.1) and ArgO of "E. coli") have been functionally characterized, but functionally uncharacterized homologues are encoded within the genomes of many bacteria including "Bacillus subtilis", "Mycobacterium tuberculosis, Aeromonas salmonicida," "Helicobacter pylori, Vibrio cholerae" and "Yersinia pestis." Thus, LysE family members are found widely distributed in Gram-negative and Gram-positive bacteria.
Structure.
These proteins are 190-240 amino acyl residues in length and possess six hydrophobic regions. PhoA fusion analyses of LysE of "C. glutamicum" provided evidence for a 5 transmembrane α-helical spanner (TMS) typology with the N-terminus inside and the C-terminus outside. However, some evidence suggests a 6 TMS topology.
Function.
LysE appears to catalyze unidirectional efflux of L-lysine (and other basic amino acids such as L-arginine), and it provides the sole route for L-lysine excretion. The energy source is believed to be the proton motive force (H+ antiport). The "E. coli" ArgO homologue (TC# 2.A.75.1.2) effluxes arginine and possibly lysine and canavanine as well.
Early studies showed that the LysE family is related to the RhtB family (TC #2.A.76) as well as the CadD family (TC #2.A.77) based both on the similar sizes and topologies of their members and on PSI-BLAST results.
Generalized Transport Reaction.
The generalized transport reaction for LysE is:
Lysine (in) + [nH+ (out) or nOH− (in)] Lysine (out) + [nH+ (in) or nOH− (out)].


OXT (gene)


High-maltose corn syrup

High-maltose corn syrup is a food additive used as a sweetener and preservative. The majority sugar is maltose. It is less sweet than high-fructose corn syrup and contains little to no fructose. It is sweet enough to be useful as a sweetener in commercial food production, however. To be given the label "high", the syrup must contain at least 50% maltose. Typically, it contains 40–50% maltose, though some have as high as 70%.
By using β-amylase or fungal α-amylase, glucose syrups containing over 50% maltose, or even over 70% maltose (extra-high-maltose syrup) can be produced.p. 465 This is possible because these enzymes remove two glucose units, that is, one maltose molecule at a time from the end of the starch molecule.
Uses.
High-maltose corn syrup is used as a substitute for normal glucose syrup in the production of hard candy: at a given moisture level and temperature, a maltose solution has a lower viscosity than a glucose solution, but will still set to a hard product. Maltose is also less humectant than glucose, so that candy produced with high-maltose syrup will not become sticky as easily as candy produced with a standard glucose syrup.p. 81
Since maltose has a low freezing point, HMCS is useful in frozen desserts. It is also used in brewing, because it has a balanced fermentability, can be added at high concentrations to the wort kettle, increasing throughput, and reduces haze caused by varying malt quality. Another of HMCS's uses is to preserve food. According to the Center for Science in the Public Interest, HMCS preserves food by inhibiting fermentation and bacterial growth.
Health effects.
In recent years, HMCS has seen an increase in use as a food additive due to the negative reputation of HFCS, as well as the absence of fructose, which is the source of the concern about the health effects of high fructose corn syrup.
High-maltose syrups produced from corn are gluten-free, but certain syrups produced from wheat or barley may contain small amounts of gluten. It is unclear whether this can have significant effects in celiac disease.


Remikiren

Remikiren is a renin inhibitor under development for the treatment of hypertension (high blood pressure). It was first developed by Hoffmann–La Roche in 1996.


C2orf73

Uncharacterized protein C2orf73 is a protein that in humans is encoded by the "C2orf73" gene. The protein is predicted to be localized to the nucleus.
Gene.
The full gene spans a total of 53,712 base pairs and contains nine exons. The gene's location in the Human genome is on chromosome 2 at position 2p16.2 and is flanked by the genes ACYP2 and SPTBN1. There are no aliases for this gene.
mRNA.
The primary mRNA produced by the C2or73 gene is 1921 nucleotides long. There are six other mRNA isoforms produced by alternative splicing and variation in exon length.
Protein.
The protein has a molecular mass of 32,142 Daltons. There are four protein isoforms. The primary isoform (X1) is 287 amino acids long.
C2orf73 contains a short sequence motif, GDWWSH (This motif does not yet have any known function). The protein is lysine rich and leucine poor compared to the content of the average Human gene and has a predicted isoelectric point of 9.305.
Structure.
A 3D structure for C2orf73 has not yet been determined experimentally. A computational prediction made by I-TASSER is presented to the right.
The PELE tool on Biology Workbench predicts three likely α-helices and one β-strand in the protein.
Post translational modifications.
The GPS, NetPhos, MyHits and SUMOsp tools on ExPASy predict potential post-translational modifications for the protein. Six potential phosphorylation sites and one sumoylation site are predicted.
Subcellular localization.
PSORT II predicts C2orf73 to be localized to the nucleus. This is supported by the predicted presence of a sumoylation site, which is involved in nuclear cytoplasmic transport.
Expression.
GEO profiles from NCBI show that C2orf73 is weakly expressed in the following tissues in Humans: bone marrow, liver, heart, lung, brain, spinal cord, skeletal muscle, thymus, and epithelium.
Regulation of expression.
The Genomatix El Dorado tool predicts many transcription factors to have a high binding affinity in the 1100 base pairs upstream of "C2orf73". Many of the transcription factors normally regulate processes such as cell development and differentiation, cell death, and the cell cycle.
Interacting Proteins.
Three proteins have been experimentally determined to interact with C2orf73 through Yeast Two-Hybrid experiments.
Function.
The function of C2orf73 is currently not well understood by the scientific community or anyone else.
Homology.
There are no paralogs of C2orf73 in the Human genome. Orthologs are found throughout, but are limited to, the phylum Chordata (with a few exceptions in other phyla of the kingdom Animalia, like the "Octopus bimaculoides").


ABCC4

ATP-binding cassette sub-family C member 4 (ABCC4), also known as the multidrug resistance-associated protein 4 (MRP4) or multi-specific organic anion transporter B (MOAT-B), is a protein that in humans is encoded by the "ABCC4" gene.
ABCC4 acts as a regulator of intracellular cyclic nucleotide levels and as a mediator of cAMP-dependent signal transduction to the nucleus. MRP4/ABCC4 also transports prostaglandins, for example PGE2, out of the cell where they can bind receptors.
MRP4/ABCC4 expression is dysregulated in several cancers and is also upregulated in peritoneal endometriosis.


Mothers against decapentaplegic homolog 5

Mothers against decapentaplegic homolog 5 also known as SMAD5 is a protein that in humans is encoded by the "SMAD5" gene.
SMAD5, as its name describes, is a homolog of the Drosophila gene: "Mothers against decapentaplegic", based on a tradition of such unusual naming within the gene research community. It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of modulators. Like many other TGFβ family members SMAD5 is involved in cell signalling and modulates signals of bone morphogenetic proteins (BMP's). The binding of ligands causes the oligomerization and phosphorylation of the SMAD5 protein. SMAD5 is a receptor regulated SMAD (R-SMAD) and is activated by bone morphogenetic protein type 1 receptor kinase. It may play a role in the pathway where TGFβ is an inhibitor of hematopoietic progenitor cells.


Vernolepin

Vernolepin is a sesquiterpene lactone isolated from the dried fruit of "Vernonia amygdalina". It shows platelet anti-aggregating properties and is also an irreversible DNA polymerase inhibitor, hence may have antitumor properties.


Nogalamycin

Nogalamycin is an anthracycline antibiotic produced by the soil bacteria "Streptomyces nogalater". It has antitumor properties but it is also highly cardiotoxic. The less cardiotoxic semisynthetic analog menogaril was developed in the 1970s. Currently nogalamycin and menogaril are not used clinically.
Biosynthesis.
Anthracycline biosynthesis involves the construction of an aglycone core (by a type II polyketide synthase) to which one or more sugar residues are attached. Nogalamycin consists of three components:
Each component is built separately and then ligated together by a two glycosyltransferases. All of the machinery associated with the biosynthesis of nogalamycin are located within the same biosynthetic gene cluster of "S. nogalater".
Nogalamycinone biosynthesis.
The biosynthetic pathway towards the aglycone core of nogalamycin has been determined by a combination of bioinformatic analysis and cloning of individual components of the biosynthetic pathway. The biosynthetic route is similar to that of aklavinone (the aglycone core of most anthracyclines, including doxorubicin), the sole difference being that the first acyl group that is loaded into the PKS is an acetate rather than a propionate. The following genes are involved in the biosynthesis of the core nogalamycinone species:
Nogalamine and nogalose biosynthesis.
The sugar moieties that are attached to nogalamycinone are produced from glucose-1-phosphate. Although the steps following dTDP-4-keto-6-deoxyglucose have not been confirmed "in vitro", the high degree of sequence similarity with homologous enzymes from other organisms suggests that the mechanism proceeds as detailed at right. The following enzymes are involved in the biosynthesis of nogalamine and nogalose:
Note that while much of the literature refers to the final, permethylated carbohydrate moiety as "nogalose", more recent data suggest that the nogalose moiety on nogalamycin is methylated after the nogalamycinone core has been glycosylated.
Nogalamycinone glycosylation and tailoring.
The most noteworthy aspect of the structure of nogalamycin is the dual attachment of nogalamine both through "O"-glycosylation and also through a carbon-carbon bond at the C2 position of the nogalamycinone core, The following enzymes are involved in the final tailoring steps of nogalamycin. "Sno"N and "sno"T are genes in the nogalamycin gene cluster that are likely to catalyze the final hydroxylation:


Cohesin domain

In molecular biology, the cohesin domain is a protein domain. It interacts with a complementary domain, termed the dockerin domain. The cohesin-dockerin interaction is the crucial interaction for complex formation in the cellulosome.
The scaffoldin component of the cellulolytic bacterium "Clostridium thermocellum" is a non-hydrolytic protein which organises the hydrolytic enzymes into a large complex, called the cellulosome. Scaffoldin comprises a series of functional domains, amongst which is a single cellulose-binding domain and nine cohesin domains which are responsible for integrating the individual enzymatic subunits into the complex.


Cloacin immunity protein

In molecular biology, the cloacin immunity protein is produced by bacteria if they contain a certain plasmid. It inhibits the bacterial polypeptide toxin, cloacin, which is produced by the same or other bacteria. It complexes with cloacin in equimolar quantities and inhibits it by binding with high affinity to the cloacin C-terminal catalytic domain. The immunity protein is relatively small, containing 85 amino acids. An extra ribosome binding site has been found to precede the immunity gene on the polycistronic Clo DF13 mRNA, which perhaps accounts for the fact that, in cloacinogenic cells, more immunity protein than cloacin is synthesised. Comparison of the complete amino acid sequence of the Clo DF13 immunity protein with that of the Col E3 and Col E6 immunity proteins reveals extensive similarities in primary structure, although Col E3 and Clo DF13 immunity proteins are exchangeable only to a low extent "in vivo" and "in vitro".


Chloramphenicol phosphotransferase-like protein family

In molecular biology, the chloramphenicol phosphotransferase-like protein family includes the chloramphenicol 3-O phosphotransferase (CPT) expressed by "Streptomyces venezuelae". Chloramphenicol (Cm) is a metabolite produced by this bacterium that can inhibit ribosomal peptidyl transferase activity and therefore protein production. By transferring a phosphate group to the C-3 hydroxyl group of Cm, CPT inactivates this potentially lethal metabolite.


Meglumine

Meglumine is an amino sugar derived from glucose. It is often used as an excipient in pharmaceuticals and in conjunction with iodinated compounds in contrast media such as diatrizoate meglumine, iothalamate meglumine and iodipamide meglumine.


Stigmastanol

Stigmastanol (sitostanol) is a phytosterol found in a variety of plant sources. Similar to sterol esters and stanol esters, stigmastanol inhibits the absorption of cholesterol from the diet. Animal studies suggest that it also inhibits biosynthesis of cholesterol in the liver.
Stigmastanol is the product of the reduction of β-sitosterol and the hydrogenation of stigmasterol.


DPNH-coenzyme Q reductase

DPNH-coenzyme Q reductase may refer to:


ProP (transporter)

ProP is a bacterial membrane protein that is a member of the major facilitator superfamily. It functions as an osmosensory and osmoregulatory transporter, responding to changes in osmotic pressure by importing compatible solutes such as proline or glycine betaine; most substrates for ProP are zwitterions. The activity of ProP increases with osmotic pressure in cells and proteoliposomes. ProP is a symporter of hydrogen ions and compatible solutes, and is responsive to potassium concentrations.
Activity of ProP has been associated with the ability of pathogenic "E. coli" to colonize the urinary tract.


GTPase-activating protein

GTPase-activating proteins or GTPase-accelerating proteins (GAPs) are a family of regulatory proteins whose members can bind to activated G proteins and stimulate their GTPase activity, with the result of terminating the signaling event. GAPs are also known as RGS protein, or RGS proteins, and these proteins are crucial in controlling the activity of G proteins. Regulation of G proteins is important because these proteins are involved in a variety of important cellular processes. The large G proteins, for example, are involved in transduction of signaling from the G protein-coupled receptor for a variety of signaling processes like hormonal signaling, and small G proteins are involved in processes like cellular trafficking and cell cycling. GAP's role in this function is to turn the G protein's activity off. In this sense, GAPs function is opposite to that of guanine nucleotide exchange factors (GEFs), which serve to enhance G protein signaling.
Mechanism.
GAP are heavily linked to the G-protein linked receptor family. The activity of G proteins comes from their ability to bind guanosine triphosphate (GTP). Binding of GTP inherently changes the activity of the G proteins and increases their activity, through the loss of inhibitory subunits. In this more active state, G proteins can bind other proteins and turn on downstream signalling targets. This whole process is regulated by GAPs, which can down regulate the activity of G proteins.
G proteins can weakly hydrolyse GTP, breaking a phosphate bond to make GDP. In the GDP-bound state, the G proteins are subsequently inactivated and can no longer bind their targets. This hydrolysis reaction, however, occurs very slowly, meaning G proteins have a built-in timer for their activity. G proteins have a window of activity followed by slow hydrolysis, which turns them off. GAP accelerates this G protein timer by increasing the hydrolytic GTPase activity of the G proteins, hence the name GTPase-activating protein.
It is thought that GAPs serve to make GTP on the G protein a better substrate for nucleophilic attack and lower the transition state energy for the hydrolysis reaction. For example, many GAPs of the small G proteins have a conserved finger-like domain, usually an arginine finger, which changes the conformation of the GTP-bound G protein to orient the GTP for better nucleophilic attack by water. This makes the GTP a better substrate for the reaction. Similarly, GAPs seem to induce a GDP-like charge distribution in the bound GTP. Because the change in charge distribution makes the GTP substrate more like the products of the reaction, GDP and monophosphate, this, along with opening the molecule for nucleophilic attack, lowers the transition state energy barrier of the reaction and allows GTP to be hydrolyzed more readily. GAPs, then, work to enhance the GTP hydrolysis reaction of the G proteins. By doing so, they accelerate the G protein's built-in timer, which inactivates the G proteins more quickly, and along with the inactivation of GEFs, this keeps the G protein signal off. GAPs, then, are critical in the regulation of G proteins.
Specificity to G proteins.
In general, GAPs tend to be pretty specific for their target G proteins. The exact mechanism of target specificity is not fully known, but it is likely that this specificity comes from a variety of factors. At the most basic level, GAP-to-G protein specificity may come simply from the timing and location of protein expression. RGS9-1, for example, is specifically expressed in the rod and cone photoreceptors in the eye retina, and is the only one to interact with G proteins involved in phototransduction in this area. A certain GAP and a certain G protein happen to be expressed in the same time and place, and that is how the cell ensures specificity. Meanwhile, scaffold proteins can also sequester the proper GAP to its G protein and enhance the proper binding interactions. These binding interactions may be specific for a particular GAP and G protein. Also, GAPs may have particular amino acid domains that recognize only a particular G protein. Binding to other G proteins may not have the same favorable interactions, and they therefore do not interact. GAPs can, therefore, regulate specific G proteins.
Examples and classification.
EIF5 is a GTPase-activating protein. Furthermore, YopE is a protein domain that is a Rho GTPase-activating protein (GAP), which targets small GTPases such as RhoA, Rac1, and Rac2.
Monomeric.
The GAPs that act on small GTP-binding proteins of the Ras superfamily have conserved structures and use similar mechanisms,
An example of a GTPase is the monomer Ran, which is found in the cytosol as well as the nucleus. Hydrolysis of GTP by Ran is thought to provide the energy needed to transport nuclear proteins into the cell. Ran is turned on and off by GEFs and GAPs, respectively.
Heterotrimeric.
Most GAPs that act on alpha subunits of heterotrimeric G proteins belong to a distinct family, the RGS protein family.
Regulation.
While GAPs serve to regulate the G proteins, there is also some level of regulation of the GAPs themselves. Many GAPs have allosteric sites that serve as interfaces with downstream targets of the particular path that they regulate. For example, RGS9-1, the GAP in the photoreceptors from above, interacts with cGMP phosphodiesterase (cGMP PDE), a downstream component of phototransduction in the retina. Upon binding with cGMP PDE, RGS9-1 GAP activity is enhanced. In other words, a downstream target of photoreceptor-induced signaling binds and activates the inhibitor of signaling, GAP. This positive regulatory binding of downstream targets to GAP serves as a negative feedback loop that eventually turns off the signaling that was originally activated. GAPs are regulated by targets of the G protein that they regulate.
There are also examples of negative regulatory mechanisms, where downstream targets of G protein signaling inhibit the GAPs. In G protein-gated potassium channels, phosphatidylinositol 3, 4, 5-triphosphate (PIP3) is a downstream target of G protein signaling. PIP3 binds and inhibits the RGS4 GAP. Such inhibition of GAP may perhaps "prime" the signaling pathway for activation. This creates a window of activity for the G proteins once activated because the GAP is temporarily inhibited. When the potassium channel is activated, Ca2+ gets released and binds calmodulin. Together, they displace PIP3 from GAP by binding competitively to the same site, and by doing so, they reactivate GAP to turn G protein signaling off. This particular process demonstrates both inhibition and activation of GAP by its regulators. There is cross-talk between GAP and other components of the signaling pathway that regulate the activity of GAP.
There have been some findings suggesting the possibility of crosstalk between GAPs. A recent study showed that the p120Ras GAP could bind the DLC1 Rho GAP at its catalytic domain. The binding of the Ras GAP to the Rho GAP inhibits the activity of the Rho GAP, thereby activating the Rho G protein. One GAP serves as a negative regulator of another GAP. The reasons for such cross-regulation across GAPs are yet unclear, but one possible hypothesis is that this cross-talk across GAPs attenuates the "off" signal of all the GAPs. Although the p120Ras GAP is active, therefore inhibiting that particular pathway, other cellular processes can still continue because it inhibits other GAPs. This may ensure that the whole system does not shut down from a single "off" signal. GAP activity is highly dynamic, interacting with many other components of signaling pathways.
Disease associations and clinical relevance.
The importance of GAPs comes from its regulation of the crucial G proteins. Many of these G proteins are involved in cell cycling, and as such are known proto-oncogenes. The Ras superfamily of G proteins, for example, has been associated with many cancers because Ras is a common downstream target of many growth factors like FGF, or fibroblast growth factor. Under normal conditions, this signaling ultimately induces regulated cell growth and proliferation. However, in the cancer state, such growth is no longer regulated and results in the formation of tumors. Often, this oncogenic behavior is due to a loss of function of GAPs associated with those G proteins or a loss of the G protein's ability to respond to its GAP. With the former, G proteins are unable to hydrolyze GTP quickly, resulting in sustained expression of the active form of G proteins. Although the G proteins have weak hydrolytic activity, in the presence of functional GEFs, the inactivated G proteins are constantly replaced with activated ones because the GEFs exchange GDP for GTP in these proteins. With no GAPs to curb the G protein's activity, this results in constitutively active G proteins, unregulated cell growth, and the cancerous state. In the case of the latter, a loss of the G protein's ability to respond to GAP, the G proteins have lost their ability to hydrolyze GTP. With a nonfunctional G protein enzyme, GAPs cannot activate the GTPase activity, and the G protein is constitutively on. This also results in unregulated cell growth and cancer.
Examples of GAP malfunction are ubiquitous clinically. Some cases involve a decreased expression of the GAP gene. For example, some recently characterized cases of papillary thyroid cancer cells in patients show a decreased expression of Rap1GAP, and this expression is seemingly caused by a decreased expression of the GAP mRNA, shown by qRT-PCR experiments. In this case, there appears to be a loss of proper Rap1GAP gene expression. In another case, expression of the Ras GAP is lost in several cancers due to improper epigenetic silencing of the gene. These cells have CpG methylations near the gene that, in effect, silence gene transcription. Regulation of G proteins is lost because the regulator is absent, resulting in cancer.
Other cancers show a loss of sensitivity of the G protein to the GAPs. These G proteins acquire missense mutations that disrupt the inherent GTPase activity of the proteins. The mutant G proteins are still bound by GAPs, but enhancing GTPase activity by the GAPs is meaningless when GTPase activity of the G protein itself is lost. GAP works to activate a nonfunctional hydrolytic enzyme. T24 bladder cancer cells, for example, were shown to have a missense mutation, G12V, resulting in constitutively active Ras protein. Despite the presence of the G protein regulator, regulation is lost due to a loss of function in the G protein itself. This loss of function also manifests itself in cancer. GAPs and their interaction with G proteins are, therefore, highly important clinically and are potential targets for cancer therapies.


Neoconvalloside

Neoconvalloside is a cardenolide glycoside extracted from "Convallaria majalis".