Enzyme zinc-dependent

Matrix metalloproteinases Zinc-dependent enzymes capable of degrading extracellular matrix proteins, including connective tissue. 

Before our work [39], only one catalytic mechanism for zinc dependent HDACs has been proposed in the literature, which was originated from the crystallographic study of HDLP [47], a histone-deacetylase-like protein that is widely used as a model for class-I HDACs. In the enzyme active site, the catalytic metal zinc is penta-coordinated by two asp residues, one histidine residues as well as the inhibitor [47], Based on their crystal structures, Finnin et al. [47] postulated a catalytic mechanism for HDACs in which the first reaction step is analogous to the hydroxide mechanism for zinc proteases zinc-bound water is a nucleophile and Zn2+ is five-fold coordinated during the reaction process. However, recent experimental studies by Kapustin et al. suggested that the transition state of HDACs may not be analogous to zinc-proteases [48], which cast some doubts on this mechanism. 

The recruitment of zinc for a structural role, or to activate an enzyme, has been observed. The zinc ion induces the dimerization of human growth hormone (hGH), with two Zn ions associated per dimer of hGH. This is confirmed by replacement of possible zinc binding residues resulting in weakened binding of the zinc ion. Formation of a zinc-hGH dimeric complex may be important for storage of hGH in secretory granules.975 In a toxic role, anthrax lethal factor is one of the three components of the secreted toxin and is a zinc-dependent protease that cleaves a protein kinase and causes lysis of macrophages.976... 

Many proteins, including many enzymes, contain hghtly bound metal ions. These may be inhmately involved in enzyme catalysis or may serve a purely structural role. The most common tightly bound metal ions found in metalloproteins include copper (Cu+ and Cu +), zinc (Zn +), iron (Fe + and Fe +), and manganese (Mn +). Other proteins may contain weakly bound metal ions that generally serve as modulators of enzyme activity. These include sodium (Na+), potassium (K+), calcium (Ca +), and magnesium (Mg +). There are also exotic cases for which enzymes may depend on nickel, selenium, molybdenum, or silicon for activity. These account for the very small requirements for these metals in the human diet. 

The equilibrium of reversible histone lysine acetylation is maintained by histone deacetylases (H D ACs) on one hand and histone acetyltransferases on the other hand. Human histone deacetylases can be separated into four classes [15]. HDACs of class I, II and IV are zinc-dependent amidohydrolases, whereas class III HDACs, also referred to as sirtuins, have a mechanism that is dependent on NAD [16]. As histone deacetylases have been widely studied, it is not surprising that there are also a large number of assays existing that have helped to characterize modulators of these enzymes and subsequently the enzymes themselves. 

In humans, 18 HDACs have been identified and classified according to their homology to yeast HDACs [6]. Class I, II and IV HDACs are zinc-dependent enzymes, whereas the third class (sirtuins) are NAD -dependent enzymes and are covered elsewhere in this book. Class I (H DACs 1, 2, 3, 8) are closely related to yeast Rpd3 class Ila (HDACs 4, 5, 7, 9) and class Ilb (HDACs 6, 10) are related to yeast Hdal and this latter subclass contains two catalytic sites. Finally, class IV H DACs contain just one member (HDAC 11). Whilst classes I and IV HDACs are mainly found in the nucleus of cells, class II H DACs are free to shuttle between the nucleus and the cytoplasm. The exact physiological role of each of the individual H DAC isoforms in cells is far from fully understood, yet it is known that these enzymes act on many other nonhistone substrates. They also often function as part of larger multiprotein complexes and are frequently associated with other HDAC isoforms and/or require the presence of several coregulators. 

This zinc-dependent enzyme [EC 3.4.15.1] (also known as dipeptidyl carboxypeptidase I, dipeptidyl-dipeptidase A, kininase II, peptidase P, and carboxycathepsin) catalyzes the release of a C-terminal dipeptide at a neutral pH. The enzyme will also act on bradykinin. The presence of prolyl residues in angiotensin I and in bradykinin results in only single dipeptides being released due to the activity of this enzyme, a protein which belongs to the peptidase M2 family. The enzyme is a glycoprotein, generally membrane-bound, that is chloride ion-dependent. 

This enzyme [EC 3.4.24.21] is a zinc-dependent digestive endopeptidase from the cardia of the crayfish Astacus... 

This enzyme [EC 4.2.1.1], also referred to as carbonate dehydratase, is a zinc-dependent enzyme that catalyzes the reaction of carbon dioxide with water to form carbonic acid (or, of bicarbonate and a proton). See also Proton Transfer in Aqueous Solution Manometric Assay Methods Marcus Rate Theory... 

This zinc-dependent enzyme [EC 3.4.17.1], a member of the peptidase family M14, catalyzes the hydrolysis of peptide bonds at the C-terminus of polypeptides. Little hydrolytic action occurs if the C-terminal amino acid is aspartate, glutamate, arginine, lysine, or proline. Car-boxypeptidase A is formed from a precursor protein, procarboxypeptidase A. 

This enzyme [EC 3.4.17.3] (also referred to as lysine carboxypeptidase, arginine carboxypeptidase, kininase I, or anaphylatoxin inactivator) is a zinc-dependent member of peptidase family M14. The enzyme hydrolyzes the peptide bond at the C-terminus provided that the C-terminal amino acid is either arginine or lysine. The enzyme inactivates bradykinin and anaphylatoxins in blood plasma. 

This enzyme [EC 3.4.13.3] (also referred to as Xaa-His dipeptidase, X-His dipeptidase, aminoacylhistidine dipeptidase, and homocarnosinase), is a zinc-dependent dipeptidase that catalyzes the hydrolysis of Xaa-His dipeptides. Carnosine, homocarnosine, and anserine are preferred substrates for this mammalian cytosolic enzyme. Other aminoacylhistidine dipeptides are weaker substrates (including homoanserine). The enzyme is activated by thiols and inhibited by metal-chelating agents. O. W. Griffith (1986) Ann. Rev. Biochem. 55, 855. 

There are many dipeptidases [EC 3.4.13.x]. Cytosol nonspecific dipeptidase [EC 3.4.13.18] (also referred to as peptidase A, glycylglycine dipeptidase, glycylleucine dipeptidase, and A -)3-alanylarginine dipeptidase) catalyzes the hydrolysis of dipeptides. Membrane dipeptidase [EC 3.1.13.19] (also known as microsomal dipeptidase, renal dipeptidase, and dehydropeptidase I) is a zinc-dependent enzyme (a member of the peptidase family M19) that also catalyzes the hydrolysis of dipeptides. 

This zinc-dependent enzyme [EC 3.4.24.15], also referred to as thimet oligopeptidase and soluble metalloendopep-tidase, catalyzes the hydrolysis of peptide bonds with a preferential cleavage at positions with hydrophobic residues at PI, P2, and P3 and a small amino acid residue at PI. Substrates for this enzyme contain five to fifteen amino acid residues. 

This zinc-dependent enzyme [EC 3.4.24.56], a member of the peptidase family M16, catalyzes the degradation of insulin, glucagon, and other polypeptides. 

Zinc-dependent enzymes [EC 3.5.2.6], including penicillinase and cephalosporinase, with varying specificity in their catalysis of j8-lactam hydrolysis. Some act more readily on penicillins, whereas the catalysis of others is more efficient with cephalosporins. 

This zinc-dependent enzyme [EC 3.4.11.1], also referred to as cytosol aminopeptidase, leucyl aminopeptidase, and peptidase S, catalyzes the hydrolysis of a terminal peptide bond such that there is a release of an N-terminal amino acid, Xaa-Xbb-, in which Xaa is preferably a leucyl residue, but may be other aminoacyl residues including prolyl (although not arginyl or lysyl). Xbb may be prolyl. In addition, amino acid amides and methyl esters are also readily hydrolyzed, but the rates with arylamides are exceedingly slow. The enzyme is activated by heavy metal ions. 

This zinc-dependent enzyme [EC 5.3.1.8] (also known as phosphomannose isomerase, phosphohexoisomerase, and phosphohexomutase) catalyzes the interconversion of D-mannose 6-phosphate and o-fructose 6-phosphate. 

These zinc-dependent endopeptidases (meprin A [EC 3.4.24.18] and meprin B [EC 3.4.24.63] ) are members of the peptidase family M12A. They catalyze the hydrolysis of peptide bonds in proteins and peptide substrates. Meprin A, a membrane-bound enzyme that has been isolated from mouse and rat kidney and intestinal brush borders as well as salivary ducts, acts preferentially on carboxyl side of hydrophobic amino acyl residues. Meprin A and B are insensitive to inhibition by phosphora-midon and thiorphan. 

This zinc-dependent enzyme [EC 2.8.1.2] catalyzes the reaction of 3-mercaptopyruvate with cyanide to produce pyruvate and thiocyanate. Other substrates include sulfite, sulfinates, mercaptoethanol, and mercaptopyruvate. 

This zinc-dependent enzyme [EC 3.1.4.3] (also known as lipophosphodiesterase I, lecithinase C, Clostridium welchii ce-toxin, and Clostridium oedematiens 13- and y-toxins) catalyzes the hydrolysis of a phosphatidylcholine to produce 1,2-diacylglycerol and choline phosphate. The enzyme isolated from bacterial sources also acts on sphingomyelin and phosphatidylinositol however, the enzyme isolated from seminal plasma does not act on phosphatidylinositol. See Micelle... 

SOLUBILITY PRODUCT Zinc carbonate monohydrate (ZnC03-H20), SOLUBILITY PRODUCT Zinc-dependent enzymes,... 

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