Substrate/ligand/inhibitor specificity

Substrate/ligand/inhibitor specificity at optimized conditions... 

Enzymes, composed of various amino acids, constitute hydrophobic interior and hydrophilic exterior by arranging in space the appropriate amino acid residues. The hydrophobic receptor site is usually located inside and the hydrophilic amino acid residues located on the surface of enzyme are heavily solvated by water molecules in aqueous solution. Then, the supramolecular interactions with specific coenzymes, substrates, and inhibitors inevitably accompany extensive dehydration and conformational change of both enzyme and ligand. 

Imidazole also acts as a substrate-competitive inhibitor, forming both binary complexes with LADH, and ternary complexes in the presence of coenzyme. X-Ray studies show that imidazole also binds to the. catalytic zinc by displacing the water molecule.1361 The presence of imidazole at the active site also enhances the rate of carboxymethylation14658 of Cys-46 with both iodoacetate and iodoacetamide.1420 This enhancement of alkylation has become known as the promotion effect .1421 Imidazole promotion also improves the specificity of the alkylation.1422 Since Cys-46 is thought to be alkylated as a metal-thiol complex, imidazole, on binding the active site metal, could enhance the reactivity by donating a electrons to the metal atom, which distributes the increased electron density further to the other ligands in the coordination sphere. The increased nucleophilicity of the sulfur results in promoted alkylation.1409... 

Considering the big variety of proton emitters and detectors, it is not difficult to insert such informative molecules as inhibitors, activators, substrate, or ligands into specific sites in proteins, membranes, or nucleic acids and study directly the role of water and proton in biochemistry. 

Effects of the substrates and Inhibitors of DHFR on the activity of GSH were examined to test whether GSH Is also related to DHFR by ligand specificity or not. GSH was potently Inhibited by... 

Some of the mechanisms underlying the physiological responses listed in Table III are given in Table IV. Enzyme destruction, which will not be considered further, occurs of course by proteolytic breakdown and, in that it can be Impeded by ligands (either substrates or inhibitors) that bind to the protein, could be subject to a specific control. Proteolysis might be enhanced by factors that activate proteases or release protease inhibitors. 

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