Enkephalinase inhibitor

An enkephalinase inhibitor is a type of enzyme inhibitor which inhibits one or more members of the enkephalinase class of enzymes that break down the endogenous enkephalin opioid peptides. Examples include racecadotril, ubenimex (bestatin), RB-101, and -phenylalanine, as well as the endogenous opioid peptides opiorphin and spinorphin. Analgesic, anticraving, antidepressant, anxiolytic, and antidiarrheal effects are common properties of enkephalinase inhibitors.


Sandhoff disease

Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.
Symptoms.
Sandhoff disease symptoms are clinically indeterminable from Tay–Sachs disease. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age. The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development. If the children had the ability to sit up by themselves or crawl they will lose this ability. This is caused by a slow deterioration of the muscles in the child’s body from the buildup of GM2 gangliosides. Since the body is unable to create the enzymes it needs within the central nervous system, it is unable to attach to these gangliosides to break them apart and make them non-toxic. With this buildup there are several symptoms that begin to appear such as muscle/motor weakness, sharp reaction to loud noises, blindness, deafness, inability to react to stimulants, respiratory problems and infections, mental retardation, seizures, cherry red spots in the retina, enlarged liver and spleen (hepatosplenomegaly), pneumonia, or bronchopneumonia.
The other two forms of Sandhoff disease have similar symptoms but to a lesser extent. Adult and juvenile forms of Sandhoff disease are more rare than the infantile form. In these cases victims suffer cognitive impairment (retardation) and a loss of muscle coordination that impairs and eventually destroys their ability to walk; the characteristic red spots in the retina also develop. The adult form of the disease, however, is sometimes milder, and may only lead to muscle weakness that impairs walking or the ability to get out of bed.
Causes.
Two parents carrying a mutated gene and passing it on to their offspring cause the disease. Even with both parents carrying the disease in their genome, there is only a 25% chance that they will have a child containing the genetic coding for the disease (see figure right).
Each form of the disease is caused by the differences in the various mutations of the genome, in particular the codons on the 14 exons in the HEX B gene located within chromosome 5 (see figure bottom), leading to the differences in severities of the symptoms. The difference in the codons has the consequence of inhibiting two enzymes located in the lysosomes of the neurons of the central nervous system. Lysosomes contain various enzymes to break down byproducts and toxins to ensure they do not accumulate enough to interfere with the function of the central nervous system.
Using restriction enzymes, it was discovered that a mutation on chromosome 5 particularly within the C1214T allele caused the adult onset form of Sandhoff Disease. For the patient showing symptoms of the infantile or juvenile form they have a mutation on exon I207V from their father, and a 16 base pair deletion from their mother which can be located on as many as five exons, exons 1–5.
Mutations and polymorphism.
Articles regarding Sandhoff disease frequencies among distinct groups of people contain discrepancies from one another. More than 25 mutations have been reported other than novel mutations.
One article says that Sandhoff disease is found commonly in individuals with a non-Jewish descent.
Others say that it is more commonly in:
Discovery of several mutations in Ashkenazi Jews may reflect ascertainment bias rather than a high population frequency, because Ashkenazi Jews were the targeted population in a mass screening program for Tay-Sachs disease. Several rare SD mutations were discovered as researchers resolved cases of enzyme deficiency among suspected TSD carriers, but no cases of the disease itself have been reported.
However, since it is an autosomal recessive disease, it is likely found in any ethnic group passing from generation to generation through carriers without being expressed in their offspring. Even though the family may not have a history of Sandhoff disease, it is possible for two individuals to have a child with the disease. Since Sandhoff disease was only discovered in 1968, there are years the disease has gone undetected because of misdiagnoses.
Pathophysiology.
Biallelic pathogenic variants in the "HEXB" gene cause Sandhoff disease. The gene provides instructions for making a protein crucial to the enzymes beta-hexosaminidase A and beta-hexosaminidase B, which function in nerve cells to break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A breaks down a fatty compound called GM2 ganglioside. Mutations in the "HEXB" gene disrupt the activity of these enzymes, preventing the breakdown of GM2 ganglioside and other molecules.
As a result, progressive damage caused by the resulting buildup of GM2 ganglioside leads to the destruction of nerve cells, causing the signs and symptoms associated with Sandhoff disease.
Diagnosis.
Sandhoff disease can be detected through the following procedures (before it is apparent through physical examination): a biopsy removing a sample of tissue from the liver, genetic testing, molecular analysis of cells and tissues (to determine the presence of a genetic metabolic disorder), enzyme assay, and occasionally a urinalysis to determine if the above-noted compounds are abnormally stored within the body. For a child to suffer from this disease, both parents must be carriers, and both must transmit the mutation to the child. Thus, even in the case where both parents have the mutation, there is only a 25 percent chance their child will inherit the condition. Frequently, parents are given the opportunity to have a DNA screening if they are at high risk, to determine their carrier status before they have children. However, it is also highly recommended to undergo testing even for those parents who do not have a family history of Sandhoff disease. Over 95% of the families that have children with Sandhoff disease had no known prior family history of the condition, as the mutation in the "HEXB" gene does not cause clinical symptoms when only one copy is present, and often passed undetected from one generation to the next Naturally, if an individual carries the mutation, he or she has a risk of transmitting it to the unborn child. Genetic counseling is recommended for those who have the mutation.
It is possible for parents who are about to have a child or had a child with Sandhoff Disease can have a PGD or PEGD. PEGD is pre-embryonic genetic diagnosis for the parents that would not benefit from a pre-implantation genetic diagnosis because of their religion or negative attitude for the discarding of embryos. PEGD sequences the genome of the embryo to be produced by two parents if they were to conceive a child. If the family has a history of Sandhoff disease it is recommended they have their genome sequenced to ensure they are not carriers or to sequence the genome of their child.
Types.
There are three types of Sandhoff disease: classic infantile, juvenile, and adult late onset. Each form is classified by the severity of the symptoms as well as the age at which the patient shows these symptoms.
Juvenile and adult onset forms of Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Sandhoff disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease.
Treatment.
Currently Sandhoff disease does not have any standard treatment and does not have a cure. However, a person suffering from the disease needs proper nutrition, hydration, and maintenance of clear airways. To reduce some symptoms that may occur with Sandhoff disease, the patient may take anticonvulsants to manage seizures or medications to treat respiratory infections, and consume a precise diet consisting of puree foods due to difficulties swallowing. Infants with the disease usually die by the age of 3 due to respiratory infections. The patient must be under constant surveillance because they can suffer from aspiration or lack the ability to change from the passageway to their lungs versus their stomach and their spit travels to the lungs causing bronchopneumonia. The patient also lacks the ability to cough and therefore must undergo a treatment to shake up their body to remove the mucus from the lining of their lungs. Medication is also given to patients to lessen their symptoms including seizures.
Currently the government is testing several treatments including N-butyl-deoxynojirimycin in mice, as well as stem cell treatment in humans and other medical treatments recruiting test patients. A Sandhoff disease study showing proof of principle for gene therapy in a human model system using CRISPR and virus gene correction gives the chance for clinical trials to cure the disease. The ultra-rare occurrence is a main hurdle to overcome for clinical trials.
History.
Sandhoff disease is one of several forms of what was formerly known as amaurotic idiocy. This inherited disease is characterized by the accumulation of lipid-containing cells in the viscera and in the nervous system, mental retardation, and impaired vision or blindness. The chemical and enzymatic analysis of various patients with amaurotic idiocy by Konrad Sandhoff (1939- ), a German biochemist, led to the identification of several biochemically distinct diseases: The first biochemical description of GM1-gangliosidosis in 1963, Sandhoff disease in 1968, Tay-Sachs-Disease, the AB-variant of GM2-Gangliosidosis and the B1-variant of GM2-gangliosidosis.
The molecular defect in Sandhoff disease was discovered when Konrad Sandhoff studied the biochemistry of sphingolipids and gangliosides in the laboratory of Prof. Horst Jatzkewitz (1912–2002), a German biochemist (Max- Planck-Institute for Psychiatry, Munich). In October 1966, he obtained deep-frozen autopsy material from an infantile case with amaurotic idiocy. The glycolipid analysis soon demonstrated differences from all the cases studied before. Besides the neuronal storage of GM2, the storage of GA2 was much more pronounced, and different from all cases of Tay-Sachs disease studied so far, globoside accumulated in the visceral organs and, most importantly, hexosaminidase activity was almost completely absent. The disease causing catabolic enzyme deficiency of hexosaminidases was demonstrated with four different substrates (p–nitrophenyl-β-D-N-acetylglucosaminide, p-nitrophenyl-β-D-N-acetylgalactosaminide, glycolipid [3H]GA2 and [3H]globoside) in four different organs and published in 1968.
References.
"This article incorporates some public domain text from The U.S. National Library of Medicine"


Catalase-related immune-responsive domain

In molecular biology, the catalase-related immune-responsive domain is a protein domain found in catalases. This domain carries the immune-responsive amphipathic octa-peptide that is recognised by T cells.


Inorganic phosphate transporter family

The inorganic phosphate transporter (PiT) family is a group of carrier proteins derived from Gram-negative and Gram-positive bacteria, archaea, and eukaryotes.
Function.
Functionally-characterized members of the family appear to catalyze inorganic phosphate (Pi) or inorganic sulfate uptake either by H+ or Na+ symport. Both PitA (TC# 2.A.20.1.1) and PitB (TC# 2.A.20.1.2) of "E. coli" probably catalyze metal ion·phosphate:H+ symport, where Mg2+, Ca2+ or Zn2+ (and probably other divalent cations) can complex with Pi. The mammalian proteins (i.e., TC# 2.A.20.2.7) have been reported to function as viral receptors, but they undoubtedly function as transport proteins as well. For numerous gammaretroviruses, such as the gibbon ape leukemia virus, woolly monkey virus, feline leukemia virus subgroup B, feline leukemia virus subgroup T, and 10A1 murine leukemia virus, this receptor is the human type III sodium-dependent inorganic phosphate transporter, SLC20A1, also known as PiT1.
The malaria parasite, "Plasmodium falciparum", grows within its host erythrocyte and induces an increase in the permeability of the erythrocyte membrane to a range of solutes including Na+ and K+. This results in a progressive increase in the concentration of Na+ in the erythrocyte cytosol. The parasite cytosol has a relatively low Na+ concentration, generating a large inward Na+ gradient across the parasite plasma membrane. Saliba et al. (2006) showed that the parasite exploits the Na+ electrochemical gradient to energize the uptake of inorganic phosphate (Pi) with a stoichiometry of 2Na+:1Pi and with an apparent preference for the monovalent over the divalent form of Pi (see TC #2.A.20.2.5).
The generalized transport reactions possibly catalyzed by members of the PiT family are:
Structure.
The molecular sizes of Pit family members are reported to vary from 354 to 681 residues (10-12 TMSs) with the mammalian and "Plasmodium" proteins exhibiting the largest sizes. The sulfate permease of "B. subtilis", CysP, is of 354 residues with 11 putative TMSs. As of early 2016, it appears no crystal structures are available for PiT proteins.
Phylogeny.
Phylogenetic grouping of the phosphate transport proteins generally correlates with organismal phylogeny. Thus the fungal, plant, animal and archaeal proteins each cluster separately. However, the tree exhibits two clusters of bacterial phosphate transport proteins. One bacterial cluster is distant from the eukaryotic proteins while the other cluster is close to the plant proteins. Both clusters include proteins from Gram-negative and Gram-positive bacteria. The sulfate permease, CysP (TC# 2.A.20.4.1), is distantly related to the phosphate permeases.
Members of the PiT family arose by a tandem internal gene duplication event. Surprisingly, TopPred predicts a 12 TMS topology for the yeast Pho89 protein, but the homologous regions are not predicted to show similar topological features.


Chloride anion exchanger

Chloride anion exchanger, also known as down-regulated in adenoma (protein DRA), is a protein that in humans is encoded by the "SLC26A3" gene.
Function.
Protein DRA is a membrane protein in intestinal cells. It is an anion exchanger and a member of the sulfate anion transporter (SAT) family. It mediates chloride and bicarbonate exchange and additionally transports sulfate and other anions at the apical membrane, part of the plasma membrane of enterocytes. It is different from the anion exchanger that present in erythrocytes, renal tubule, and several other tissues.
The protein encoded by this gene is a transmembrane glycoprotein that functions as a sulfate transporter. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells, and is instrumental in chloride reuptake, aiding in the creation of an osmotic gradient for resorption of fluid from the lumen of the intestine.
Clinical significance.
Mutations in this gene have been associated with congenital chloride diarrhoea, a treatable disease.
The congenital absence of this membrane protein results in an autosomal recessive disorder called congenital chloridorrhea or congenital chloride diarrhea (CLD).


Acireductone dioxygenase

Acireductone dioxygenase may refer to:


Fructan beta-fructosidase

Fructan beta-fructosidase (, "exo-beta-D-fructosidase", "exo-beta-fructosidase", "polysaccharide beta-fructofuranosidase", "fructan exohydrolase") is an enzyme with systematic name "beta-D-fructan fructohydrolase". This enzyme catalyses the following chemical reaction
Hydrolyses inulin and levan, and also sucrose.


TRIM62

TRIM62, also called DEAR1 (for ductal epithelium–associated RING chromosome 1), is a protein in the tripartite motif family. In human it is encoded by the gene "TRIM62". "TRIM62" is involved in the morphogenesis of the mammary gland, and loss of "TRIM62" gene expression in breast is associated with a higher risk of recurrence in early-onset breast cancer.


Thiamine transporter

Members of this protein family have been assigned as thiamine transporters by a phylogenomic analysis of families of genes regulated by the THI element, a broadly conserved RNA secondary structure element through which thiamine pyrophosphate (TPP) levels can regulate transcription of many genes related to thiamine transport, salvage, and de novo biosynthesis. Species with this protein always lack the ThiBPQ ABC transporter. In some species (e.g. "Streptococcus mutans" and "Streptococcus pyogenes"), is the only THI-regulated gene. Evidence from "Bacillus cereus" indicates thiamine uptake is coupled to proton translocation.
This family includes human solute transporters SLC19A1, SLC19A2 and SLC19A3.


AMPT

Alpha-methyl-"p"-tyrosine (AMPT) is a tyrosine hydroxylase enzyme inhibitor and is therefore a drug involved in inhibiting the catecholamine biosynthetic pathway. AMPT inhibits tyrosine hydroxylase whose enzymatic activity is normally regulated through the phosphorylation of different serine residues in regulatory domain sites. Catecholamine biosynthesis starts with dietary tyrosine, which is hydroxylated by tyrosine hydroxylase and it is hypothesized that AMPT competes with tyrosine at the tyrosine-binding site, causing inhibition of tyrosine hydroxylase.
It has been used in the treatment of pheochromocytoma. It has been demonstrated to inhibit the production of melanin.
Pharmacology.
Effect on catecholamine biosynthesis.
AMPT inhibits catecholamine biosynthesis at the first step—the hydroxylation of tyrosine. Reduction in catecholamines and their metabolites (normetanephrine, metanephrine, and 4-hydroxy-3-methoxymandelic acid) result from the inhibition of tyrosine using AMPT. AMPT doses of 600 to 4,000 mg per day cause a 20 to 79 percent reduction in total catecholamines in Pheochromocytoma patients. Increase in dosage increases the magnitude of catecholamine synthesis inhibition. This increasing inhibitory effect is seen in dosages up to 1500 mg per day; at higher doses, the inhibitory effect of AMPT decreases. The maximum effect of orally administered AMPT occurs 48 to 72 hours after administration of the drug. Catecholamine production levels return to normal 72 to 96 hours after administration of the drug ceases. Dosages as low as 300 mg per day have been found to have an effect on catecholamine production, which can be measured through urinary excretion analysis and cerebral spinal fluid assays.
AMPT is successful at inhibiting catecholamine production in humans whether the rate of synthesis is high, as in pheochromocytoma, or normal as in patients with hypertension.
Effect on blood pressure.
Pheochromocytoma patients exhibited a drop in blood pressure when taking AMPT. AMPT had no effect in patients with hypertension (high blood pressure).
Pharmacokinetics.
Absorption
AMPT is minimally metabolized by the body and absorbed well after oral ingestion making its bioavailability high. Single-dose studies have shown that a 1,000 mg dose results in AMPT levels in the plasma of 12-14 µg/mL after 1 to 3 hours of ingestion. Maintenance-dose studies have shown that absorption of AMPT is overall the same in all individuals taking doses in the range of 300-4,000 mg per day.
Half-life
The half-life of AMPT in normal patients is 3.4 to 3.7 hours. In amphetamine addicts the half-life is 7.2 hours.
Elimination
Small amounts of metabolites (alpha-methyldopa and alpha-methyldopamine) were found after the administration of both single-doses and maintenance-doses of AMPT. Small amounts of methyltyramine and alpha-methylnoradrenaline were found in patients undergoing AMPT therapy. Urine analysis also recovered 45 to 88 percent of unchanged AMPT after drug ingestion. Of the total AMPT excreted, 50 to 60 percent appeared in urine within the first 8 hours and 80 to 90 percent appeared within 24 hours of oral administration.
Medical Use.
Pheochromocytoma
Pheochromocytoma is a rare neuroendocrine tumor that results in the release of too much epinephrine and norepinephrine, hormones that control heart rate, metabolism, and blood pressure. AMPT was used in the 1960s for preoperative pharmacological control of catecholamine overexpression that causes hypertension and other arterial and cardiac abnormalities. The use of AMPT to treat Pheochromocytoma prior to surgery was discontinued due to its extensive side effects.
Drug Interactions
"Psychosis"-
Phosphorylation of tyrosine hydroxylase at Ser31 or Ser40 can increase dopamine biosynthesis; therefore an increase in pSer31 or pSer40 elevates dopamine synthesis in DA neurons. Excessive dopamine in the mesolimbic pathways of the brain produces psychotic symptoms. Antipsychotic medications block dopamine D2 receptors in the caudate and putamen as well as in limbic target areas, they can also block or partially block serotonin. Therapy with AMPT could prove to be more specific to dopamine and therefore eliminate some of the negative side effects of antipsychotic drugs.
"Cocaine and Methamphetamines"-
The dopamine transporter (DAT) is a principal site of action for cocaine. Cocaine inhibits DAT function and vesicular dopamine transport (VMAT). Cocaine administration abruptly and reversibly increases both the Vmax of dopamine uptake and the Bmax of vesicular monoamine transporter 2 (VMAT-2) ligand (dihydrotetrabenazine) binding. Dopamine depletion resulting from administration of AMPT had similar neuropharmacological effects as cocaine. Administration of methamphetamine, a dopamine-releasing agent, rapidly decreased vesicular uptake. A relationship between cytoplasmic dopamine concentration and VMAT activity was established using cocaine, methamphetamines, and AMPT. Although it is not well understood, this relationship allows for AMPT’s inhibitory property, which blocks tyrosine hydroxylase, to increase dopamine transport by the vesicle monoamine transporter-2. This leads to a reduction in the newly synthesized pool of dopamine from replenished tyrosine. AMPT’s effect on dopamine concentration and transport is reversible and short-lived. If methamphetamine is administered while cytoplasmic dopamine is depleted to about 50% of the control levels, its neurotoxic effects are averted (Thomas et al., 2008). The recovery of dopamine to normal levels after AMPT administration takes about 2 to 7 days, and this repletion of dopamine is not changed by methamphetamine. For these reasons AMPT seems to be a better treatment drug in methamphetamine addicts than reserpine, which is also being researched as a possible methamphetamine treatment drug. Reserpine causes almost full loss of dopamine from the striatum by disrupting vesicle storage. The repletion of dopamine after reserpine administration is slower than AMPT. Additionally, administration of reserpine when dopamine is maximally depleted causes neurotoxic effects, which does not occur with AMPT treatment. AMPT’s role in addiction has also been studied via changes in dopamine binding to D2 and D3 receptors in the striatum (caudate, putamen, and ventral striatum) after the administration of AMPT. Findings revealed that cocaine-dependent subjects exhibited lower levels of endogenous dopamine relative to healthy subjects after AMPT administration. Similar positive effects were found in the role of AMPT in methamphetamine-addicted subjects.
"Dystonia and Dyskinesia"-
Dystonias and dyskinesias onset seems to derive from inconsistent regulation of dopamine in dopamine pathways. AMPT’s ability to deplete dopamine in the CNS makes it a promising target for treatment of dopamine related disorders.
Side-effects.
AMPT administration in healthy subjects has shown to cause increased sleepiness, decreased calmness, increased tension and anger, and a trend for increased depression. Sedation was also reported as a side effect of AMPT ingestion. However, sedation was not seen in AMPT doses of less than 2g per day. Patients have reported insomnia as a withdrawal symptom post AMPT exposure. When L-dopa is administered following AMPT administration, the effects of AMPT are reversed. These findings suggest that AMPT's effect on alertness and anxiety is catecholamine-specific and further supports that catecholamines are involved in the regulation of normal states of arousal and pathological anxiety symptoms. Patients have reported hand, leg, and trunk tremors as well as tightening of the jaw post AMPT drug therapy. These Parkinson like side effects are supported by the lack of dopamine in the brain as in Parkinson’s patients. Tourette syndrome patients treated with AMPT developed akinesia, akathisia, and oculogyric crisis. Most severe of all, patients developed crystalluria (crystals in the urine) after undergoing AMPT drug treatments.
Prolonged administration can have an impact upon the circadian rhythm.
Mechanism.
As a competitive inhibitor of tyrosine hydroxylase, it prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine. This results in lowered systematic catecholamine (dopamine, epinephrine and norepinephrine) levels.


N-acetyl-L-glutamate synthetase

N-acetyl-L-glutamate synthetase may refer to:


Cajeta Elegancita


2-dehydro-3-deoxygalactonokinase

In enzymology, a 2-dehydro-3-deoxygalactonokinase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ATP and 2-dehydro-3-deoxy-D-galactonate, whereas its two products are ADP and 2-dehydro-3-deoxy-D-galactonate 6-phosphate.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:2-dehydro-3-deoxy-D-galactonate 6-phosphotransferase. Other names in common use include 2-keto-3-deoxygalactonokinase, 2-keto-3-deoxygalactonate kinase (phosphorylating), and 2-oxo-3-deoxygalactonate kinase. This enzyme participates in galactose metabolism.


Plakophilin-3

Plakophilin-3 is a protein that in humans is encoded by the "PKP3" gene.
Function.
This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This protein may act in cellular desmosome-dependent adhesion and signaling pathways.
Interactions.
PKP3 has been shown to interact with:


3,4-Xylenol

3,4-Xylenol is a chemical compound which is one of the six isomers of xylenol.


2-dehydro-3-deoxy-6-phosphogalactonate aldolase

In enzymology, a 2-dehydro-3-deoxy-6-phosphogalactonate aldolase () is an enzyme that catalyzes the chemical reaction
Hence, this enzyme has one substrate, 2-dehydro-3-deoxy-D-galactonate 6-phosphate, and two products, pyruvate and D-glyceraldehyde 3-phosphate.
This enzyme belongs to the family of lyases, specifically the aldehyde-lyases, which cleave carbon-carbon bonds. The systematic name of this enzyme class is 2-dehydro-3-deoxy-D-galactonate-6-phosphate D-glyceraldehyde-3-phosphate-lyase (pyruvate-forming). Other names in common use include 6-phospho-2-keto-3-deoxygalactonate aldolase, phospho-2-keto-3-deoxygalactonate aldolase, 2-keto-3-deoxy-6-phosphogalactonic aldolase, phospho-2-keto-3-deoxygalactonic aldolase, 2-keto-3-deoxy-6-phosphogalactonic acid aldolase, (KDPGal)aldolase, 2-dehydro-3-deoxy-D-galactonate-6-phosphate, and D-glyceraldehyde-3-phosphate-lyase. This enzyme participates in galactose metabolism.
Structural studies.
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes and .


Mitochondrial carrier

Mitochondrial carriers are proteins from solute carrier family 25 which transfer molecules across the membranes of the mitochondria. Mitochondrial carriers are also classified in the Transporter Classification Database. The Mitochondrial Carrier (MC) Superfamily has been expanded to include both the original Mitochondrial Carrier (MC) family (TC# 2.A.29) and the Mitochondrial Inner/Outer Membrane Fusion (MMF) family (TC# 1.N.6).
Phylogeny.
Members of the MC family (TC# 2.A.29) are found exclusively in eukaryotic organelles although they are nuclearly encoded. Most are found in mitochondria, but some are found in peroxisomes of animals, in hydrogenosomes of anaerobic fungi, and in amyloplasts of plants.
15 paralogues of the MC family are encoded within the genome of "Saccharomyces cerevisiae." 50 have been identified in humans, 58 in "A. thaliana" and 35 in "S. cerevisiae". The functions of many of the human homologues are unknown, but most of the yeast homologues have been functionally identified. See TCDB for functional assignments
Function.
Many MC proteins preferentially catalyze the exchange of one solute for another (antiport). A variety of these substrate carrier proteins, which are involved in energy transfer, have been found in the inner membranes of mitochondria and other eukaryotic organelles such as the peroxisome and facilitate the transport of inorganic ions, nucleotides, amino acids, keto acids and cofactors across the membrane. Such proteins include:
Functional aspects of these proteins, including metabolite transport, have been reviewed by Dr. Ferdinando Palmieri and Dr. Ciro Leonardo Pierri (2010). Diseases caused by defects of mitochondrial carriers are reviewed by Palmieri et al. (2008) and by Gutiérrez-Aguilar and Baines 2013. Mutations of mitochondrial carrier genes involved in mitochondrial functions other than oxidative phosphorylation are responsible for carnitine/acylcarnitine carrier deficiency, HHH syndrome, aspartate/glutamate isoform 2 deficiency, Amish microcephaly, and neonatal myoclonic epilepsy. These disorders are characterized by specific metabolic dysfunctions, depending on the physiological role of the affected carrier in intermediary metabolism. Defects of mitochondrial carriers that supply mitochondria with the substrates of oxidative phosphorylation, inorganic phosphate and ADP, are responsible for diseases characterized by defective energy production. Residues involved in substrate binding in the middle of the transporter and gating have been identified and analyzed.
Structure.
Permeases of the MC family (the human SLC25 family) possess six transmembrane α-helices. The proteins are of fairly uniform size of about 300 residues. They arose by tandem intragenic triplication in which a genetic element encoding two spanners gave rise to one encoding six spanners. This event may have occurred less than 2 billion years ago when mitochondria first developed their specialized endosymbiotic functions within eukaryotic cells. Members of the MC family are functional and structural monomers although early reports indicated that they are dimers.
Most MC proteins contain a primary structure exhibiting three repeats, each of about 100 amino acid residues in length, and both the N and C termini face the intermembrane space. All carriers contain a common sequence, referred to as the MCF motif, in each repeated region, with some variation in one or two signature sequences.
Amongst the members of the mitochondrial carrier family that have been identified, it is the ADP/ATP carrier (AAC; TC# 2.A.29.1.1) that is responsible for importing ADP into the mitochondria and exporting ATP out of the mitochondria and into the cytosol following synthesis. The AAC is an integral membrane protein that is synthesised lacking a cleavable presequence, but instead contains internal targeting information. It consists of a basket shaped structure with six transmembrane helices that are tilted with respect to the membrane, 3 of them "kinked" due to the presence of prolyl residues.
Residues that are important for the transport mechanism are likely to be symmetrical, whereas residues involved in substrate binding will be asymmetrical reflecting the asymmetry of the substrates. By scoring the symmetry of residues in the sequence repeats, Robinson et al. (2008) identified the substrate-binding sites and salt bridge networks that are important for transport. The symmetry analyses provides an assessment of the role of residues and provides clues to the chemical identities of substrates of uncharacterized transporters.
There are structures of the mitochondrial ADP/ATP carrier in two different states. One is the cytoplasmic state, inhibited by carboxyatractyloside, in which the substrate binding site is accessible to the intermembrane space, which is confluent with the cytosol, i.e. the bovine mitochondrial ADP/ATP carrier /, the yeast ADP/ATP carrier Aac2p /, the yeast ADP/ATP carrier Aac3p /, Another is the matrix state, inhibited by bongkrekic acid, in which the substrate binding site is accessible to the mitochondrial matrix, i.e. the fungal mitochondrial ADP/ATP carrier . In addition, there are structures of the calcium regulatory domains of the mitochondrial ATP-Mg/Pi carrier in the calcium-bound state / and mitochondrial aspartate/glutamate carriers in different regulatory states //.
Substrates.
Mitochondrial carriers transport amino acids, keto acids, nucleotides, inorganic ions and co-factors through the mitochondrial inner membrane. The transporters consist of six transmembrane alpha-helices with threefold pseudo-symmetry.
The transported substrates of MC family members may bind to the bottom of the cavity, and translocation results in a transient transition from a 'pit' to a 'channel' conformation. An inhibitor of AAC, carboxyatractyloside, probably binds where ADP binds, in the pit on the outer surface, thus blocking the transport cycle. Another inhibitor, bongkrekic acid, is believed to stabilize a second conformation, with the pit facing the matrix. In this conformation, the inhibitor may bind to the ATP-binding site. Functional and structural roles for residues in the TMSs have been proposed. The mitochondrial carrier signature, Px[D/E]xx[K/R], of carriers is probably involved both in the biogenesis and in the transport activity of these proteins. A homologue has been identified in the mimivirus genome and shown to be a transporter for dATP and dTTP.
Examples of transported compounds include:
Examples.
Human proteins containing this domain include:
Yeast Ugo1 is an example of the MMF family, but this protein has no human ortholog.


Luteusin A

Luteusin A is an azaphilone monoamine oxidase inhibitor produced by "Talaromyces luteus".


Natural resistance-associated macrophage protein 2

Natural resistance-associated macrophage protein 2 (NRAMP 2), also known as divalent metal transporter 1 (DMT1) and divalent cation transporter 1 (DCT1), is a protein that in humans is encoded by the "SLC11A2" (solute carrier family 11, member 2) gene. DMT1 represents a large family of orthologous metal ion transporter proteins that are highly conserved from bacteria to humans.
As its name suggests, DMT1 binds a variety of divalent metals including cadmium (Cd2+), copper (Cu2+), and zinc (Zn2+,); however, it is best known for its role in transporting ferrous iron (Fe2+). DMT1 expression is regulated by body iron stores to maintain iron homeostasis. DMT1 is also important in the absorption and transport of manganese (Mn2+). In the digestive tract, it is located on the apical membrane of enterocytes, where it carries out H+-coupled transport of divalent metal cations from the intestinal lumen into the cell.
Function.
Iron is not only essential for the human body, it is required for all organisms in order for them to be able to grow. Iron also participates in many metabolic pathways. Iron deficiency can lead to iron-deficiency anemia thus iron regulation is very crucial in the human body.
In mammals.
The process of iron transportation consists of iron being reduced by ferrireductases that are present on the cell surface or by dietary reductants such as ascorbate (Vitamin C). Once the Fe3+ has been reduced to Fe2+, the DMT1 transporter protein transports the Fe2+ ions into the cells that line the small intestine (enterocytes). From there, the ferroportin/IREG1 transporter exports it across the cell membrane where is it oxidized to Fe3+ on the surface of the cell then bound by transferrin and released into the blood stream.
Ion selectivity.
DMT1 is not a 100% selective transporter as it also transports Zn2+, Mn2+, and Ca2+ which can lead to toxicity problems. The reason for this is because it cannot distinguish the difference between the different metal ions due to low selectivity for iron ions. In addition, it causes the metal ions to compete for transportation and the concentration of iron ions is typically substantially lower than that of other ions.
Yeast vs. mammal pathway.
The iron uptake pathway in "Saccharaomyces cerevisiae", which consists of a multicopper ferroxidase (Fet3) and an iron plasma permease (FTR1) has a high affinity for iron uptake compared to the DMT1 iron uptake process present in mammals. The iron uptake process in yeasts consists of Fe3+ which is reduced to Fe2+ by ferriductases. Ferrous iron may also be present outside of the cell due to other reductants present in the extracellular medium. Ferrous iron is then oxidized to ferric iron by Fet3 on the external surface of the cell. Then Fe3+ is transferred from Fet3 to FTR1 and transferred across the cell membrane into the cell.
Ferrous-oxidase mediated transport systems exist in order to transport specific ions opposed to DMT1, which does not have complete specificity. The Fet3/FTR1 iron uptake pathway is able to achieve complete specificity for iron over other ions due to the multi-step nature of the pathway. Each of the steps involved in the pathway is specific to either ferrous iron or ferric iron. The DMT1 transporter protein does not have specificity over the ions it transports because it is unable to distinguish between Fe2+ and the other divalent metal ions it transfer through the cell membrane. Although, the reason that non-specific ion transporters, such as DMT1, exist is due to their ability to function in anaerobic environments opposed to the Fet3/FTR1 pathway which requires oxygen as a co substrate. So in anaerobic environments the oxidase would not be able to function thus another means of iron uptake is necessary.
Role in neurodegenerative diseases.
Toxic accumulation of divalent metals, especially iron and/or manganese, are frequently discussed aetiological factors in a variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. DMT1 may be the major transporter of manganese across the blood brain barrier and expression of this protein in the nasal epithelium provides a route for direct absorption of metals into the brain. DMT1 expression in the brain may increase with age, increasing susceptibility to metal induced pathologies. DMT1 expression is found to be increased in the substantia nigra of Parkinson's patients and in the ventral mesencephalon of animal models intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - a neurotoxin widely used experimentally to produce Parkinsonian symptoms.
The DMT1 encoding gene SLC11A2 is located on the long arm of chromosome 12 (12q13) close to susceptibility regions for Alzheimer's disease and restless legs syndrome. The C allele of SNP rs407135 on the DMT1 encoding gene SLC11A2 is associated with shorter disease duration in cases of spinal onset amyotrophic lateral sclerosis, and is implicated in Alzheimer's disease onset in males as well. The CC haplotype for SNPs 1254T/C IVS34+44C/A is associated with Parkinson's disease susceptibility. Finally, variant alleles on several SLC11A2 SNPs are associated with iron anemia, a risk factor for manganese intoxication and restless legs syndrome.


2-pyrone-4,6-dicarboxylate lactonase

In enzymology, 2-pyrone-4,6-dicarboxylate lactonase () is an enzyme that catalyzes the reversible hydrolytic chemical reaction
Thus, the two substrates of this enzyme are 2-pyrone-4,6-dicarboxylate and H2O, whereas its product is a tautomeric mixture of 4-oxalomesaconate and 4-carboxy-2-hydroxymuconate.
This enzyme belongs to the Amidohydrolase superfamily of enzymes and is a member of Cluster of Orthologous Groups (COG) 3618. The systematic name of this enzyme is 2-pyrone-4,6-dicarboxylate lactonase but is also known as LigI. This enzyme is found to play an important role in the metabolism of lignin-derived aromatic compounds in both the syringate degradation pathway and the protocatechuate 4,5-cleavage pathway.
LigI from "Sphingomonas" is of particular interest as it has been shown to be the first member of the amidohydrolase superfamily to not require a divalent metal cation for catalytic activity.
Mechanism.
The mechanism of catalysis of LigI has been determined by crystallography and NMR analysis. More specifically, the hydrolytic water molecule is activated by the transfer of a proton to Asp-248 whereas the carbonyl group of the 2-pyrone-4,6-dicarboxylate (PDC) lactone substrate is activated by hydrogen bonding interactions with His-180, His-31, and His-33.


3-ketovalidoxylamine C-N-lyase

In enzymology, a 3-ketovalidoxylamine C-N-lyase () is an enzyme that catalyzes the chemical reaction
Hence, this enzyme has one substrate, 4-nitrophenyl-3-ketovalidamine, and two products, 4-nitroaniline and 5-D-(5/6)-5-C-(hydroxymethyl)-2,6-dihydroxycyclohex-2-en-1-one.
This enzyme belongs to the family of lyases, specifically amine lyases, which cleave carbon-nitrogen bonds. The systematic name of this enzyme class is 4-nitrophenyl-3-ketovalidamine 4-nitroaniline-lyase [5-D-(5/6)-5-C-(hydroxymethyl)-2,6-dihydroxycyclohex-2-en-1-one-form ing]. Other names in common use include 3-ketovalidoxylamine A C-N-lyase, p-nitrophenyl-3-ketovalidamine p-nitroaniline lyase, and 4-nitrophenyl-3-ketovalidamine 4-nitroaniline-lyase. It employs one cofactor, calcium.


Acetylmethionine sulfoxide reductase

Acetylmethionine sulfoxide reductase may refer to:


D-xylulose reductase

In enzymology, a D-xylulose reductase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are xylitol and NAD+, whereas its 3 products are D-xylulose, NADH, 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 xylitol:NAD+ 2-oxidoreductase (D-xylulose-forming). Other names in common use include NAD+-dependent xylitol dehydrogenase, xylitol dehydrogenase, erythritol dehydrogenase, 2,3-cis-polyol(DPN) dehydrogenase (C3-5), pentitol-DPN dehydrogenase, and xylitol-2-dehydrogenase. This enzyme participates in pentose and glucuronate interconversions.
Structural studies.
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code .


RB-3007

RB-3007 is an orally active analogue of RB-101. It acts as an enkephalinase inhibitor, which is used in scientific research.


4-(hydroxymethyl)benzenesulfonate dehydrogenase

In enzymology, a 4-(hydroxymethyl)benzenesulfonate dehydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 4-(hydroxymethyl)benzenesulfonate and NAD+, whereas its 3 products are 4-formylbenzenesulfonate, NADH, 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 4-(hydroxymethyl)benzenesulfonate:NAD+ oxidoreductase. This enzyme participates in 2,4-dichlorobenzoate degradation.


Cis-2,3-dihydrobiphenyl-2,3-diol dehydrogenase

In enzymology, a cis-2,3-dihydrobiphenyl-2,3-diol dehydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are cis-3-phenylcyclohexa-3,5-diene-1,2-diol and NAD+, whereas its 3 products are biphenyl-2,3-diol, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is cis-3-phenylcyclohexa-3,5-diene-1,2-diol:NAD+ oxidoreductase. This enzyme is also called 2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase. This enzyme participates in biphenyl degradation.


Benzbromarone

Benzbromarone is a uricosuric agent and non-competitive inhibitor of xanthine oxidase used in the treatment of gout, especially when allopurinol, a first-line treatment, fails or produces intolerable adverse effects. It is structurally related to the antiarrhythmic amiodarone.
Benzbromarone is highly effective and well tolerated, and clinical trials as early as 1981 and as recently as April 2008 have suggested it is superior to both allopurinol, a non-uricosuric xanthine oxidase inhibitor, and probenecid, another uricosuric drug.
Mechanism of action.
Benzbromarone is a very potent inhibitor of CYP2C9. Several analogues of the drug have been developed as CYP2C9 and CYP2C19 inhibitors for use in research.
History.
Benzbromarone was introduced in the 1970s and was viewed as having few associated serious adverse reactions. It was registered in about 20 countries throughout Europe, Asia and South America.
In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies.


Gluconate-proton symporter

The gluconate:H+ symporter (GntP) family (TC# 2.A.8) is a family of transport proteins belonging to the ion transporter (IT) superfamily. Members of the GntP family include known gluconate permeases of "E. coli" and "Bacillus" species such as the D-Gluconate:H+ symporter of "Bacillus subtillus" (GntP; TC# 2.A.8.1.1) and the D-fructuronate/D-gluconate:H+ symporter of "E. coli" (GntP; TC# 2.A.8.1.3). A representative list of proteins belonging to the GntP family can be found in the Transporter Classification Database.
Structure.
Bioinformatic analysis suggests these proteins are of about 450 residues and possess 12 or 14 putative transmembrane α-helical spanners. No crystal structure data are available for GntP proteins as of early 2016.
Function.
Four of the seven "E. coli" paralogues have been found to possess active gluconate uptake activity, and one of them (GntW; TC# 2.A.8.1.2) can accommodate both L-idonate and D-gluconate, although L-idonate is the physiological substrate. Another (GntP) transports D-gluconate with high affinity but is specifically induced by and transports D-fructuronate. GntT of "E. coli" is the physiological gluconate permease.
Transport reaction.
The generalized transport reaction catalyzed by proteins of the GntP family is:
Carbohydrate acid (out) + nH+ (out) → Carbohydrate acid (in) + nH+ (in)


Arogenate dehydrogenase

In enzymology, an arogenate dehydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are L-arogenate and NAD+, whereas its 3 products are L-tyrosine, NADH, and CO2.
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 L-arogenate:NAD+ oxidoreductase (decarboxylating). Other names in common use include arogenic dehydrogenase (ambiguous), cyclohexadienyl dehydrogenase, pretyrosine dehydrogenase (ambiguous), and L-arogenate:NAD+ oxidoreductase. This enzyme participates in phenylalanine, tyrosine and tryptophan biosynthesis and novobiocin biosynthesis.
Structural studies.
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code .


GINS (protein complex)

GINS is a protein complex essential to the DNA replication process in the cells of eukaryotes. The complex participates in the initiation and elongation stages of replication.
The name GINS is an acronym created from the first letters of the Japanese numbers 5-1-2-3 ("go-ichi-ni-san") in a reference to the 4 protein subunits of the complex: Sld5, Psf1, Psf2, and Psf3.
A similar complex has been identified in Archaea.


Glycoside hydrolase family 67

In molecular biology, glycoside hydrolase family 67 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 67 includes alpha-glucuronidases, these are components of an ensemble of enzymes central to the recycling of photosynthetic biomass, remove the alpha-1,2 linked 4-O-methyl glucuronic acid from xylans.
Members of this family consist of three structural domains. Deletion mutants of alpha-glucuronidase from "Bacillus stearothermophilus" have indicated that the central region is responsible for the catalytic activity. Within this central domain, the invariant Glu and Asp (residues 391 and 364 respectively from "Bacillus stearothermophilus") are thought to form the catalytic centre. The C-terminal region of alpha-glucuronidase is mainly alpha-helical. It wraps around the catalytic domain, making additional interactions both with the N-terminal domain of its parent monomer and also forming the majority of the dimer-surface with the equivalent C-terminal domain of the other monomer of the dimer.


List of breath mints

This is a list of breath mint brands in alphabetical order. A breath mint is a type of candy primarily consumed to freshen the smell of one's breath, by masking offensive odors with the scent of mint or other flavoring, and by stimulating the flow of saliva to help remove food and bacterial debris from the mouth. Like chewing gums and throat lozenges, many breath mints are artificially sweetened and consumed solely for non-nutritive purposes.


Fleroxacin

Fleroxacin is a quinolone antibiotic. It is sold under the brand names Quinodis and Megalocin.
Mechanism of action.
Fleroxacin is a bactericidal drug that inhibits bacterial DNA gyrase and topoisomerase IV. Like other quinolones and fluoroquinolones the compound eradicates bacteria by interfering with DNA replication (bacterial DNA replication, transcription, repair and recombination).
Fleroxacin is active against many Gram-positive and Gram-negative bacteria. It is especially active against Shigella species., Salmonella sp., Escherichia coli, Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, Yersinia enterocolitica, Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa.
Pharmacokinetics.
After oral administration fleroxacin is rapidly and well absorbed from the gastrointestinal tract and shows a good bioavailability. The antibiotic is widely distributed throughout the body and in the different biological tissues. In many biologic specimens the levels of fleroxacin are similar to those in plasma, but in bile, nasal secretions, seminal fluid, lung, bronchial mucosa, and ovaries, the drug concentrations are 2-3 times higher than those in plasma.
The serum elimination half-life, in subjects with normal renal function, is relatively long (9–12 hours), which permits once-daily dosing.
Approximately the urinary excretion is 38% of an orally administered dose within 48 h, and in urine is possible detect 8.6% of the N-demethyl metabolite and 4.4% of the N-oxide metabolite. Fleroxacin can penetrate into milk of nursing women. As quinolones are known to induce arthropathy in juvenile animals, administration of the drug to breast-feeding women cannot be allowed.
Medical uses.
Fleroxacin is effective in the treatment of a wide variety of infections, particularly uncomplicated cystitis in women, acute uncomplicated pyelonephritis, gonorrhea, bacterial enteritis, traveler's diarrhea, respiratory tract infections ( including exacerbation of chronic bronchitis).
Adverse effects.
In treated patients the most common adverse reactions are gastrointestinal, including dyspepsia, nausea, vomiting, flatulence, abdominal pain, diarrhea and sometimes constipation.
Also common disorders affecting the skin (itching, urticaria, rash, phototoxicity and photosensitivity) and central nervous system (dizziness, headache, tremor, paresthesia, impaired sense of taste and smell), psychiatric disorders (alteration of the sleep-wake cycle state of anxiety, depression, hallucinations and nightmares).
Fleroxacin and other fluoroquinolones, are known to trigger seizures or lower the seizure threshold, due to their inhibitory activity on GABA receptor binding. The antibiotic should not be administered to patients with epilepsy or a personal history of previous convulsive attacks as may promote the onset of these disorders.
Contraindications.
Fleroxacin is contraindicated in patients with a history of hypersensitivity to the substance or any other member of the quinolone class, or any component of the medicine. Fleroxacin, like other fluoroquinolones, can cause degenerative changes in weightbearing joints of young animals. The antibiotic should only be used in children when the expected benefits are outweigh the risks.


CTBP2

C-terminal-binding protein 2 also known as CtBP2 is a protein that in humans is encoded by the "CTBP2" gene.
Function.
The CtBPs - CtBP1 and CtBP2 in mammals - are among the best characterized transcriptional corepressors. They typically turn their target genes off. They do this by binding to sequence-specific DNA-binding proteins that carry a short motif of the general form Proline-Isoleucine-Aspartate-Leucine-Serine (the PIDLS motif). They then recruit histone modifying enzymes, histone deacetylases, histone methylases and histone demethylases. These enzymes are thought to work together to remove activating and add repressive histone marks. For example, histone deacetylase 1 (HDAC1) and HDAC2 can remove the activating mark histone 3 acetyl lysine 9 (H3K9Ac), then the histone methylase G9a can add methyl groups, while the histone demethylase lysine specific demethylase 1 (LSD1) can remove the activating mark H3K4me.
The CtBPs bind to many different DNA-binding proteins and also bind to co-repressors that are themselves bound to DNA-binding proteins, such as Friend of GATA (Fog). CtBPs can also dimerize and multimerize to bridge larger transcriptional complexes. They appear to be primarily scaffold proteins that allow the assembly of gene repression complexes.
One interesting aspect of CtBPs is their ability to bind to NADH and to a lesser extent NAD+. It has been proposed that this will enable them to sense the metabolic status of the cell and to regulate genes in response to changes in the NADH/NAD+ ratio. Accordingly, CtBPs have been found to be important in fat biology, binding to key proteins such as PRDM16, NRIP, and FOG2.
The full functional roles of CtBP proteins in mammals have been difficult to evaluate because of partial redundancy between CtBP1 and CtBP2. Similarly, the early lethality of the CtBP2 knockout and of double knockout mice has precluded detailed analysis of the cellular effects of deleting these proteins. Important results have emerged from model organisms where there is only a single CtBP gene. In "Drosophila" CtBP is involved in development and in circadian rhythms. In the worm "C. elegans" CtBP is involved in life span. Both circadian rhythms and life span appear to be linked to metabolism supporting the role for CtBPs in metabolic sensing.
The mammalian CtBP2 gene produces alternative transcripts encoding two distinct proteins. In addition to the transcriptional repressor (corepressor) discussed above, there is a longer isoform that is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3'-untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10.
Interactions.
CTBP2 has been shown to interact with:


SnRNP70

snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein that in humans is encoded by the "SNRNP70" gene. snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease. U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.
Interactions.
snRNP70 has been shown to interact with ASF/SF2, SRPK1, and ZRANB2.
Role in autoimmunity.
Antibodies towards snRNP70 are associated with mixed connective tissue disease.


Acyl-homoserine lactone acylase

Acyl-homoserine lactone acylase may refer to:


Raltitrexed

Raltitrexed (Tomudex, TDX, ZD 1694) is an antimetabolite drug used in cancer chemotherapy. It is an inhibitor of thymidylate synthase, and is manufactured by AstraZeneca.
Uses.
Used in treatment of colorectal cancer since 1998, it may also be used in the treatment of malignant mesothelioma. Raltitrexed is approved for use in Canada and some European countries, but is not approved by the US FDA.
Mechanism of action.
Raltitrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites, which inhibit one or more of three enzymes that use folate and derivatives as substrates: DHFR, GARFT and thymidylate synthase. Raltitrexed is fully active after polyglutamylation, which allows cellular retention of the drug.
By inhibiting Thymidylate synthase (TS), thus formation of precursor pyrimidine nucleotides, raltitrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.
Inhibition of L1210 cell growth in culture IC50 = 9 nM, is one of the strongest antimetabolites in use.
Structure and phase I clinical trial of the precursor drug, CB3717, was described in 1986.


Glycosaminoglycan

Glycosaminoglycans (GAGs) or mucopolysaccharides are long linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, with the exception of keratan, where in the place of the uronic sugar it has galactose. Because GAGs are highly polar and attract water, they are used in the body as a lubricant or shock absorber.
Mucopolysaccharidoses are a group of metabolic disorders in which abnormal accumulations of glycosaminoglycans occur because of enzyme deficiencies.
Production.
Glycosaminoglycans vary greatly in molecular mass, disaccharide construction, and sulfation. This is because GAG synthesis is not template driven like proteins or nucleic acids, but constantly altered by processing enzymes.
GAGs are classified into four groups based on core disaccharide structures. Heparin/heparan sulfate (HSGAGs) and chondroitin sulfate/dermatan sulfate (CSGAGs) are synthesized in the Golgi apparatus, where protein cores made in the rough endoplasmic reticulum are post-translationally modified with O-linked glycosylations by glycosyltransferases forming proteoglycans. Keratan sulfate may modify core proteins through N-linked glycosylation or O-linked glycosylation of the proteoglycan. The fourth class of GAG, hyaluronic acid is synthesized by integral membrane synthases which immediately secrete the dynamically elongated disaccharide chain.
HSGAG and CSGAG.
HSGAG and CSGAG modified proteoglycans first begin with a consensus Ser-Gly/Ala-X-Gly motif in the core protein. Construction of a tetrasaccharide linker that consists of -GlcAβ1–3Galβ1–3Galβ1–4Xylβ1-O-(Ser)-, where xylosyltransferase, β4-galactosyl transferase (GalTI),β3-galactosyl transferase (GalT-II), and β3-GlcA transferase (GlcAT-I) transfer the four monosaccharides, begins synthesis of the GAG modified protein. The first modification of the tetrasaccharide linker determines whether the HSGAGs or CSGAGs will be added. Addition of a GlcNAc promotes the addition of HSGAGs while addition of GalNAc to the tetrasaccharide linker promotes CSGAG development. GlcNAcT-I transfers GlcNAc to the tetrasaccahride linker, which is distinct from glycosyltransferase GlcNAcT-II, the enzyme that is utilized to build HSGAGs. EXTL2 and EXTL3, two genes in the EXT tumor suppressor family, have been shown to have GlcNAcT-I activity. Conversely, GalNAc is transferred to the linker by the enzyme GalNAcT to initiate synthesis of CSGAGs, an enzyme which may or may not have distinct activity compared to the GalNAc transferase activity of chondroitin synthase.
With regard to HSGAGs, a multimeric enzyme encoded by EXT1 and EXT2 of the EXT family of genes, transfers both GlcNAc and GlcA for HSGAG chain elongation. While elongating, the HSGAG is dynamically modified, first by N-deacetylase, N-sulfotransferase (NDST1), which is a bifunctional enzyme that cleaves the N-acetyl group from GlcNAc and subsequently sulfates the N-position. Next, C-5 uronyl epimerase coverts d-GlcA to l-IdoA followed by 2-"O" sulfation of the uronic acid sugar by 2-"O" sulfotransferase (Heparan sulfate 2-O-sulfotransferase). Finally, the 6-"O" and 3-"O" positions of GlcNAc moities are sulfated by 6-"O" (Heparan sulfate 6-O-sulfotransferase) and 3-O (3-OST) sulfotransferases.
Chondroitin sulfate and dermatan sulfate, which comprise CSGAGs, are differentiated from each other by the presence of GlcA and IdoA epimers respectively. Similar to the production of HSGAGs, C-5 uronyl epimerase converts d-GlcA to l-IdoA to synthesize dermatan sulfate. Three sulfation events of the CSGAG chains occur: 4-"O" and/or 6-"O" sulfation of GalNAc and 2-"O" sulfation of uronic acid. Four isoforms of the 4-"O" GalNAc sulfotransferases (C4ST-1, C4ST-2, C4ST-3, and D4ST-1) and three isoforms of the GalNAc 6-"O" sulfotransferases (C6ST, C6ST-2, and GalNAc4S-6ST) are responsible for the sulfation of GalNAc.
Keratan sulfate types.
Unlike HSGAGs and CSGAGs, the third class of GAGs, those belonging to keratan sulfate types, are driven towards biosynthesis through particular protein sequence motifs. For example, in the cornea and cartilage, the keratan sulfate domain of aggrecan consists of a series of tandemly repeated hexapeptides with a consensus sequence of E(E/L)PFPS. Additionally, for three other keratan sulfated proteoglycans, lumican, keratocan, and mimecan (OGN), the consensus sequence NX(T/S) along with protein secondary structure was determined to be involved in "N"-linked oligosaccharide extension with keratan sulfate. Keratan sulfate elongation begins at the nonreducing ends of three linkage oligosaccharides, which define the three classes of keratan sulfate. Keratan sulfate I (KSI) is "N" -linked via a high mannose type precursor oligosaccharide. Keratan sulfate II (KSII) and keratan sulfate III (KSIII) are "O"-linked, with KSII linkages identical to that of mucin core structure, and KSIII linked to a 2-"O" mannose. Elongation of the keratan sulfate polymer occurs through the glycosyltransferase addition of Gal and GlcNAc. Galactose addition occurs primarily through the β-1,4-galactosyltransferase enzyme (β4Gal-T1) while the enzymes responsible for β-3-Nacetylglucosamine have not been clearly identified. Finally, sulfation of the polymer occurs at the 6-position of both sugar residues. The enzyme KS-Gal6ST (CHST1) transfers sulfate groups to galactose while N-acetylglucosaminyl-6-sulfotransferase (GlcNAc6ST) (CHST2) transfers sulfate groups to terminal GlcNAc in keratan sulfate.
Hyaluronic acid.
The fourth class of GAG, hyaluronic acid, is not sulfated and is synthesized by three transmembrane synthase proteins HAS1, HAS2, and HAS3. HA, a linear polysaccharide, is composed of repeating disaccharide units of →4)GlcAβ(1→3)GlcNAcβ(1→ and has a very high molecular mass, ranging from 105 to 107 Da. Each HAS enzyme is capable of transglycosylation when supplied with UDP-GlcA and UDP-GlcNAc. HAS2 is responsible for very large hyaluronic acid polymers, while smaller sizes of HA are synthesized by HAS1 and HAS3. While each HAS isoform catalyzes the same biosynthetic reaction, each HAS isoform is independently active. HAS isoforms have also been shown to have differing "K"m values for UDP-GlcA and UDPGlcNAc. It is believed that through differences in enzyme activity and expression, the wide spectrum of biological functions mediated by HA can be regulated, such as its involvement with neural stem cell regulation in the subgranular zone of the brain.
Function.
CSGAGs interact with heparin binding proteins, specifically dermatan sulfate interactions with fibroblast growth factor FGF-2 and FGF-7 have been implicated in cellular proliferation and wound repair while interactions with hepatic growth factor/scatter factor (HGF/SF) activate the HGF/SF signaling pathway (c-Met) through its receptor. CASGAGs are important in providing support and adhesiveness in bone, skin, and cartilage. Other biological functions for which CSGAGs are known to play critical functions in include inhibition of axonal growth and regeneration in CNS development, roles in brain development, neuritogenic activity, and pathogen infection.
Dermatan sulfates
Dermatan sulfates function in the skin, tendons, blood vessels, and heart valves.
Classification.
Members of the glycosaminoglycan family vary in the type of hexosamine, hexose or hexuronic acid unit they contain (e.g. glucuronic acid, iduronic acid, galactose, galactosamine, glucosamine).
They also vary in the geometry of the glycosidic linkage.
Examples of GAGs include:


Aspergillopeptidase A

Aspergillopeptidase A may refer to:


Ethyl decanoate

Ethyl decanoate, also known as ethyl caprate, is a fatty acid ester formed from capric acid and ethanol. This ester is a frequent product of fermentation during winemaking, especially at temperatures above 15°C.


Glycoside hydrolase family 56

In molecular biology, glycoside hydrolase family 56 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 56 CAZY GH_56 includes enzymes with hyaluronidase activity. The venom of "Apis mellifera" (Honeybee) contains several biologically-active peptides and two enzymes, one of which is a hyaluronidase. The amino acid sequence of bee venom hyaluronidase contains 349 amino acids, and includes four cysteines and a number of potential glycosylation sites. The sequence shows a high degree of similarity to PH-20, a membrane protein of mammalian sperm involved in sperm-egg adhesion, supporting the view that hyaluronidases play a role in fertilisation.
PH-20 is required for sperm adhesion to the egg zona pellucida; it is located on both the sperm plasma membrane and acrosomal membrane. The amino acid sequence of the mature protein contains 468 amino acids, and includes six potential N-linked glycosylation sites and twelve cysteines, eight of which are tightly clustered near the C-terminus.


Charleston Chew

Charleston Chew is a candy bar consisting of flavored nougat covered in chocolate flavor coating. It was created in 1925 by the Fox-Cross Candy Company, founded by stage actor Donley Cross and his friend Charlie Fox. The candy was named after the Charleston, a popular dance at that time.
History.
The company was purchased in 1957 by Nathan Sloane and later sold to Nabisco in 1980. Although Sloane did not invent the Charleston Chew, he did change the candy's original form, chocolate-covered vanilla nougat. In the 1970s, he introduced such new flavors as chocolate and strawberry. Warner-Lambert purchased Charleston Chew from RJR Nabisco in 1988, then Tootsie Roll Industries purchased the brand from Warner-Lambert in 1993.
Flavors and varieties.
The candy is available in vanilla, chocolate, and strawberry flavors. At one time, there were three additional flavours; banana, grape, and cherry. "Mini Charleston Chews" are a bite-sized, similarly-shaped version of the candy bar, introduced in 1998. The original packaging for Charleston Chews was a grey box that had the brand name in a small red font at the bottom of the box.
In science and technology demonstrations.
Charleston Chew candy bars have been used to demonstrate rheology to students in North American university geology labs.


Prosaposin

Prosaposin, also known as PSAP, is a protein which in humans is encoded by the "PSAP" gene.
This highly conserved glycoprotein is a precursor for 4 cleavage products: saposins A, B, C, and D. Saposin is an acronym for Sphingolipid Activator PrO[S]teINs. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities.
Saposins A–D are required for the hydrolysis of certain sphingolipids by specific lysosomal hydrolases.
Structure.
Every saposin contains about 80 amino acid residues and has six equally placed cysteines, two prolines, and a glycosylation site (two in saposin A, one each in saposins B, C, and D). Since saposins characteristics of extreme heat-stability, abundance of disulfide linkages, and resistance to most proteases, they are assumed to be extremely compact and rigidly disulfide-linked molecules. Each saposin has an α-helical structure that is seen as being important for stimulation because this structure is maximal at a pH of 4.5; which is optimal for many lysosomal hydrolases. This helical structure is seen in all (especially with the first region), but saposin has been predicted to have β-sheet configuration due to it first 24 amino acids of the N-end.
Function.
They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble degradative enzymes. which contains four "Saposin-B domains", yielding the active saposins after proteolytic cleavage, and two "Saposin-A domains" that are removed in the activation reaction. The Saposin-B domains also occur in other proteins, many of them active in the lysis of membranes.
Clinical significance.
Mutations in this gene have been associated with Gaucher disease, Tay–Sachs disease, and metachromatic leukodystrophy.


Glycoside hydrolase family 65

In molecular biology, glycoside hydrolase family 65 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.
This family of glycosyl hydrolases (CAZY GH_65) includes vacuolar acid trehalase and maltose phosphorylases. Maltose phosphorylase (MP) is a dimeric enzyme that catalyzes the conversion of maltose and inorganic phosphate into beta-D-glucose-1-phosphate and glucose.
It consists of three structural domains. The C-terminal domain forms a two layered jelly roll motif. This domain is situated at the base of the catalytic domain, however its function remains unknown. The central domain is the catalytic domain, which binds a phosphate ion that is proximal the highly conserved Glu. The arrangement of the phosphate and the glutamate is thought to cause nucleophilic attack on the anomeric carbon atom. The catalytic domain also forms the majority of the dimerisation interface. The N-terminal domain is believed to be essential for catalytic activity although its precise function remains unknown.


Mothers against decapentaplegic homolog 2

Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the "SMAD2" gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the "Drosophila" gene 'mothers against decapentaplegic' (Mad) and the "C. elegans" gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.
Function.
SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the cell nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants encoding the same protein have been observed.
Like other Smads, Smad2 plays a role in the transmission of extracellular signals from ligands of the Transforming Growth Factor beta (TGFβ) superfamily of growth factors into the cell nucleus. Binding of a subgroup of TGFβ superfamily ligands to extracellular receptors triggers phosphorylation of Smad2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its extreme C-terminus. Phosphorylated Smad2 is then able to form a complex with Smad4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression.
Nomenclature.
The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the "C. elegans" protein SMA. The name is a combination of the two. During "Drosophila" research, it was found that a mutation in the gene "MAD" in the mother repressed the gene "decapentaplegic" in the embryo. The phrase "Mothers against" was added, since mothers often form organizations opposing various issues, e.g., Mothers Against Drunk Driving, or (MADD). The nomenclature for this protein is based on a tradition of such unusual naming within the gene research community.
Interactions.
Mothers against decapentaplegic homolog 2 has been shown to interact with:


Altoids

Altoids are a brand of mints, sold primarily in distinctive metal tins. The brand was created by the London-based Smith & Company in the 1780s, and became part of the Callard & Bowser company in the 19th century. Their advertising slogan is "The Original Celebrated Curiously Strong Mints", referring to the high concentration of peppermint oil used in the original flavour lozenge. The name "Altoids" is derived from the Latin “alt” (to change) and the Greek “oids” (taking the form of); the mints were originally conceived as a lozenge intended to relieve intestinal discomfort.
Marketing.
Altoids are less widely available in the United Kingdom, their country of origin, than in the US. The mints are stocked in Morrisons. Marks & Spencer produces a near identical product called "Curiously Strong Mints". Unlike their marketing in the US, Altoids have never been heavily marketed in the UK. Callard & Bowser-Suchard once manufactured Altoids at a plant in Bridgend, Wales, but has since moved production to a Mars Wrigley plant in Chattanooga, Tennessee, United States, in order to manufacture the products closer to where they are primarily marketed. They were marketed for a brief period in the 1990s under the "Nuttall's" brand when Callard and Bowser was under the ownership of Terry's.
Flavours and varieties.
Mints.
, Altoids mints are available in four flavours: peppermint, wintergreen, spearmint, and cinnamon. "Sugar-Free Smalls", tiny square mints sweetened with sorbitol and sucralose, are also available in peppermint, wintergreen, and cinnamon. In 2007, dark chocolate-dipped mints were introduced in three flavours: peppermint, cinnamon and ginger and in 2008, dark chocolate-dipped mints were introduced in crème de menthe. The chocolate-dipped varieties were discontinued in 2010. Also historically made but no longer available were liquorice, cool honey, and (non-chocolate dipped) ginger and crème de menthe varieties. Circa early 2011, Altoids altered the ingredients of their Wintergreen mints, adding blue food colouring. Altoid mints other than those labelled "sugar-free smalls" contain gelatin.
Sours.
Sour hard sweets in round tins were introduced in 2001 but were discontinued in 2010 due to low sales. Flavours included raspberry, citrus, apple, tangerine, and mango. Limited edition passion fruit sours were also released around Valentine's Day in 2005 in a larger 2.3 oz tin instead of the standard 1.76 oz sours tins that had been released up until then.
Gum.
The sugar-free chewing gum, introduced in 2003, was made in the United States. Flavors include peppermint, cinnamon, spearmint, wintergreen and two sour flavours, cherry and apple. The gum has not been seen in stock in US stores since January 2010 and has been discontinued.
Altoids Strips.
In 2003, breath strips in peppermint and cinnamon flavors were introduced. They were discontinued.
Altoids Arctic.
In 2014, Eclipse Mints, another Wrigley product, were re-branded as Altoids Arctic, with the tin remaining identical save for labelling. The re-branded mints were released in only Peppermint, Wintergreen, and Strawberry, doing away with the wider varieties of Eclipse such as Cinnamon, Winterfrost, and several other flavors, as well as the chewable. As before, each tin contains 1.2 oz (34g), or about 50 mints.
Tins.
The distinctive tins in which Altoids mints are packaged are often reused for other purposes. They have long been used as containers for household items like paper clips, coins, sewing materials and other small items.
The tins are sometimes used to house electronics projects. BeagleBone, a single-board computer made by Texas Instruments, is deliberately shaped with rounded corners to fit inside the tin.
A Retrocomputing hobbyist computer, the RCA 1802-based Membership Card microcomputer kit, is designed to fit in an Altoids tin, and CMoy pocket headphone amplifiers often use the containers as an enclosure.
Altoids tins have also been popular with outdoor enthusiasts for many years as first-aid or mini survival kit containers. A name for these kits is "Bug-Out Altoids Tins", or "BOATs".
Two hobbyist's by the names of Wermy and Helder have created a kit that allows you to use an Altoids tin as a portable retro gaming machine, called the mintyPi.
Altoids Award.
At the grand opening of The New Museum of Contemporary Art in 2007, Altoids announced the biennial Altoids Award. A cash prize of is awarded to four individual artists from around the US. Winners have their art exhibited at the museum after the rigorous selection process is completed. The first winners were chosen by Paul McCarthy, Cindy Sherman, and Rirkrit Tiravanija.


ERP44

Endoplasmic reticulum resident protein 44 (ERp44) also known as thioredoxin domain-containing protein 4 (TXNDC4) is a protein that in humans is encoded by the "ERP44" gene.
Interactions.
TXNDC4 has been shown to interact with ERO1L.


Sialoadhesin

Sialoadhesin is a cell adhesion molecule found on the surface of macrophages. It is found in especially high amounts on macrophages of the spleen, liver, lymph node, bone marrow, colon, and lungs. Also, in patients suffering from rheumatoid arthritis, the protein has been found in great amounts on macrophages of the affected tissues. It is defined as an I-type lectin, since it contains 17 immunoglobulin (Ig) domains (one variable domain and 16 constant domains), and thus also belongs to the immunoglobulin superfamily (IgSF). Sialoadhesin binds to certain molecules called sialic acids. During this binding process a salt bridge (protein) is formed between a highly conserved arginine residue (from the v-set domain to the 3'-sialyllactose) and the carboxylate group of the sialic acid. Since sialoadhesin binds sialic acids with its N-terminal IgV-domain, it is also a member of the SIGLEC family. Alternate names for sialoadhesin include siglec-1 and CD169 (cluster of differentiation 169).
Sialoadhesin predominantly binds neutrophils, but can also bind monocytes, natural killer cells, B cells and a subset of cytotoxic T cells by interacting with sialic acid molecules in the ligands on their surfaces.
Sialoadhesin (CD169) positive macrophages, along with mesenchymal stem cells and beta-adrenergic neurons, form the hematopoietic stem cell niche in the bone marrow. CD169+ macrophages mediate signaling between the various cells and seem to promote hematopoietic stem cell retention to the niche.


Holin superfamily V

The Holin superfamily V is a superfamily of integral membrane transport proteins. It is one of the seven different holin superfamilies in total. In general, these proteins are thought to play a role in regulated cell death, although functionality varies between families and individual members. The Holin superfamily V includes the TC families:
Superfamily V includes protein families classified in the Transporter Classification Database as TC# 1.E.21 and TC# 1.E.29. Both families possess members from "Firmicutes", "Actinobacteria" and "Chloroflexi". Proteins of this superfamily all appear to have 3 transmembrane segments (TMSs) and have average sizes of 97 and 101 amino acyl residues (aas), respectively.


3-oxoacid CoA-transferase

In enzymology, a 3-oxoacid CoA-transferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are succinyl-CoA and 3-oxo acid, whereas its two products are succinate and 3-oxoacyl-CoA.
This enzyme belongs to the family of transferases, specifically the CoA-transferases. The systematic name of this enzyme class is succinyl-CoA:3-oxo-acid CoA-transferase. Other names in common use include 3-oxoacid coenzyme A-transferase, 3-ketoacid CoA-transferase, 3-ketoacid coenzyme A transferase, 3-oxo-CoA transferase, 3-oxoacid CoA dehydrogenase, acetoacetate succinyl-CoA transferase, acetoacetyl coenzyme A-succinic thiophorase, succinyl coenzyme A-acetoacetyl coenzyme A-transferase, and succinyl-CoA transferase. This enzyme participates in 3 metabolic pathways: synthesis and degradation of ketone bodies, valine, leucine and isoleucine degradation, and butanoate metabolism.
This protein may use the morpheein model of allosteric regulation.
Structural studies.
As of late 2007, 7 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , and .


Actinidain

Actinidain (, "actinidin", "Actinidia anionic protease", "proteinase A2 of Actinidia chinensis") is a type of cysteine protease enzyme found in fruits including kiwifruit (genus "Actinidia"), pineapple, mango, banana and papaya. This enzyme is part of the papain-like peptidase C1 family.
As a known allergen in kiwifruit, the enzyme is under preliminary research for its effect on tight junction proteins of intestinal epithelial cells.
Actinidain is commercially useful as a meat tenderiser and in coagulating milk for dairy products. The denaturation temperature of actinidain is , lower than that of similar meat tenderising enzymes bromelain from pineapple and papain from papaya.


Estradiol monopropionate

Estradiol propionate (EP), also known as estradiol monopropionate or estradiol 17β-propionate and sold under the brand names Acrofollin, Akrofollin, and Follhormon, is an estrogen medication and estrogen ester which is no longer marketed. It is the C17β propionate ester of estradiol. EP was provided in an oil solution and was administered by intramuscular injection. The medication was first marketed by 1938 or 1939.


Lyxose

Lyxose is an aldopentose — a monosaccharide containing five carbon atoms, and including an aldehyde functional group. It has chemical formula 5105. It is a C'-2 carbon epimer of the sugar xylose.
Lyxose occurs only rarely in nature, for example, as a component of bacterial glycolipids.


Amifloxacin

Amifloxacin is a fluoroquinolone antibiotic, which is similar in its activity to ciprofloxacin.


Juglanin

Juglanin is a flavonol found in "Polygonum aviculare".


8-amino-7-oxononanoate synthase

In enzymology, a 8-amino-7-oxononanoate synthase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 6-carboxyhexanoyl-CoA and L-alanine, whereas its 3 products are 8-amino-7-oxononanoate, CoA, and CO2.
This enzyme participates in biotin metabolism. It employs one cofactor, pyridoxal phosphate.
Nomenclature.
This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is 6-carboxyhexanoyl-CoA:L-alanine C-carboxyhexanoyltransferase (decarboxylating). Other names in common use include 7-keto-8-aminopelargonic acid synthetase, 7-keto-8-aminopelargonic synthetase, and 8-amino-7-oxopelargonate synthase.


Acyl-CoA oxidase

In enzymology, an acyl-CoA oxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are acyl-CoA and O2, whereas its two products are trans-2,3-dehydroacyl-CoA and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with oxygen as acceptor. The systematic name of this enzyme class is acyl-CoA:oxygen 2-oxidoreductase. Other names in common use include fatty acyl-CoA oxidase, acyl coenzyme A oxidase, and fatty acyl-coenzyme A oxidase. This enzyme participates in 3 metabolic pathways: fatty acid metabolism, polyunsaturated fatty acid biosynthesis, and ppar signaling pathway. It employs one cofactor, FAD.
Structural studies.
As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes , , , , , and .


Small acidic protein

Small acidic protein is a protein that in humans is encoded by the "SMAP" gene.


8-oxocoformycin reductase

In enzymology, a 8-oxocoformycin reductase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are coformycin and NADP+, whereas its 3 products are 8-oxocoformycin, 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 coformycin:NADP+ 8-oxidoreductase. This enzyme is also called 8-ketodeoxycoformycin reductase.


Lefty (protein)

Lefty (left-right determination factors) are a class of proteins that are closely related members of the TGF-beta superfamily of growth factors. These proteins are secreted and play a role in left-right asymmetry determination of organ systems during development. Mutations of the genes encoding these proteins have been associated with left-right axis malformations, particularly in the heart and lungs.
History.
Lefty, a divergent member of the transforming growth factor-β (TGF beta) superfamily of proteins, was originally discovered in the Hamada lab at the Osaka University using deletion screening of cDNA libraries in P19 embryonic carcinoma cells to find clones that did not differentiate when induced to differentiate using retinoic acid. From these screens, researchers found one gene that was a tentative member of the TGF-beta superfamily that was predominantly expressed on the left side the embryo and aptly named it lefty. Like other members of the TGF-beta superfamily, lefty is synthesized as a preproprotein, meaning that the protein is proteolytically cleaved and excreted to produce the active form of the protein. However, lefty has only 20-25% sequence similarity with other members of the TGF-beta superfamily. Lefty is conserved in all vertebrates and many species have more than one homologue. Humans and mice, for instance have two homologues, Lefty 1 and Lefty 2, whose differential expression leads to distinct purposes while the mechanism of action is conserved.
Function.
Lefty proteins function as an antagonist of the Nodal Signaling pathway. Nodal is another signaling protein which is responsible for gastrulation, left-right patterning and induction of the primitive node. As NODAL protein diffuse through an embryo, it triggers Nodal Signaling within tissues with the required receptors and coreceptors. Activated nodal signaling leads to the transcription of the lefty gene. The protein is then expressed, proteolytically cleaved, and finally secreted. Secreted lefty binds to EGF-CFC proteins like one-eyed pinhead in zebrafish keeping the essential cofactor from associating with NODAL/ Activin-like receptor complex. This will effectually block Nodal Signaling. During induction of the primitive streak, lefty confines Nodal activity to the posterior end of the embryo, establishing a posterior signaling center and inducing the formation of the primitive streak and mesoderm. (See Nodal Signaling or TGF beta signaling pathway for more information on the nodal signaling pathway.)
There are many differences between the left and right sides, including heart and lung positioning. Mutations in these genes cause incorrect positioning of these organs (e.g., situs inversus), or in the case of constitutively inactive lefty, the embryo becomes entirely mesoderm and fails to pattern or develop. During vertebrate development, lefty proteins regulate left-right asymmetry by controlling the spatiotemporal influence of the NODAL protein. Lefty1 in the ventral midline prevents the Cerberus (paracrine factor or "Caronte") signal from passing to the right side of the embryo. This spatiotemporal control is achieved by using two sources of excreted lefty. While lefty is produced in response to activated nodal signaling, it is also produced and secreted in the anterior visceral endoderm (AVE). The balance of lefty from the AVE and from Nodal Signaling results in the patterning of the embryo and left-right asymmetry.
Clinical significance.
Proper functioning of Lefty is crucial to the proper development of the heart, lungs, spleen, and liver. Mutations in Lefty, called Lefty-A, are associated with left-right patterning defects. This mutation may cause congenital heart defects due to malformation, interrupted inferior vena cava, and lack of lung asymmetry (left pulmonary isomerism). Lefty2 may play a role in endometrial bleeding.
Lefty-1.
Lefty-1 is a regulatory gene that plays a vital role in the determination of the left-right internal asymmetry observed in mammals. The lefty-1 protein works in tandem with two other genes: lefty-2 and nodal. As the primitive node migrates towards the cranial end of the embryo during development, its cilia preferentially sling lefty-2 and nodal towards the left side of the embryo. These two genes encode for “leftness”, and initiate the formation of the heart, spleen, and other internal organs that are found on the left side in a typical human being. Lefty-1 protein can be viewed as a barrier between the left and right portions of the embryo that prevents the diffusion of lefty-2 and nodal to the right side. This ensures that the left-determining molecules are confined to their correct developmental domain. A variety of defects were observed in mice that had lefty-1 deleted, including left pulmonary isomerism, situs inversus, and atrial septal defect [2]. The high incidence of left pulmonary isomerism in the knockout mice indicates that lefty-1 itself is not involved in encoding for leftness, but simply ensures the correct compartmentation of the left-determining molecules. In the absence of the lefty-1 barrier, lefty-2 and nodal are free to diffuse to the right side and initiate the development of a left lung that was meant to be limited to the left side of the thoracic cavity.


Plakophilin-4

Plakophilin-4 is a protein that in humans is encoded by the "PKP4" gene.
Function.
Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants have been found for this gene, but the full-length nature of only two of them have been described so far. These two variants encode distinct isoforms.
Interactions.
PKP4 has been shown to interact with:


(R)-6-hydroxynicotine oxidase

In enzymology, a (R)-6-hydroxynicotine oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are (R)-6-hydroxynicotine, HO, and O, whereas its two products are 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one and HO.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as acceptor. The systematic name of this enzyme class is (R)-6-hydroxynicotine:oxygen oxidoreductase. Other names in common use include D-6-hydroxynicotine oxidase, and 6-hydroxy-D-nicotine oxidase. It employs one cofactor, FAD.
Structural studies.
As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes , , and .


Benzoyl-CoA 3-monooxygenase

In enzymology, a benzoyl-CoA 3-monooxygenase () is an enzyme that catalyzes the chemical reaction:
The 4 substrates of this enzyme are benzoyl-CoA, NADPH, H+, and O2, whereas its 3 products are 3-hydroxybenzoyl-CoA, NADP+, and H2O.
This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as one donor, and incorporation of one atom o oxygen into the other donor. The systematic name of this enzyme class is benzoyl-CoA,NADPH:oxygen oxidoreductase (3-hydroxylating). This enzyme is also called benzoyl-CoA 3-hydroxylase.