Proteins, direct ligands, catalytic

Proteins as Direct Ligands for Catalytic Metal Ions. 48... 

In different catalytic active CAs, Trp is conserved at position 97, while any one of the hydrophobic amino acids (Phe, Leu, lie, Met) is retained at positions 93 and 95. It has been proposed that these hydrophobic shell residues enhance protein-metal affinity by establishing a metal site environment with a reduced dielectric constant (123). The direct and indirect ligands are invariant in all sequenced and catalytically active a-CAs (103a). 

Studies of the oxidation of organic sulfides with amino acid-derived ligands in acetonitrile revealed very little difference between the mechanism of their oxidation and that of halides, except for one major exception. Despite the fact that acid conditions are still required for the catalytic cycle, hydroxide or an equivalent is not produced in the catalytic cycle, so no proton is consumed [48], As a consequence, there is no requirement for maintenance of acid levels during a catalyzed reaction. Peroxo complexes of vanadium are well known to be potent insulin-mimetic compounds [49,50], Their efficacy arises, at least in part, from an oxidative mechanism that enhances insulin receptor activity, and possibly the activity of other protein tyrosine kinases activity [51]. With peroxovanadates, this is an irreversible function. Apparently, there is no direct effect on the function of the kinase, but rather there is inhibition of protein tyrosine phosphatase activity. The phosphatase regulates kinase activity by dephosphorylating the kinase. Oxidation of an active site thiol in the phosphatase prevents this down-regulation of kinase activity. Presumably, this sulfide oxidation proceeds by the process outlined above. 

All chemical reactions in a biological cell take place with the direct participation of enzymes as catalysts. Enzymes are proteins, which are macromolecules composed of a combination of the 20 amino acids. Enzymes, as catalysts, are highly efficient and selective in binding small molecular species called ligands. A ligand that is acted upon by an enzyme to cause a chemical reaction is called a substrate. Only a certain, small portion of the amino acids that comprise an enzyme is involved in the catalytic reaction. This region is called the active site, and is directly involved in the formation of product(s). For example, the amino acid residues of proteins are greatly influenced by their local pH values, and the activity of proton acceptors and donors occurs in the active site. 

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