Hydrophobicity contrast, metal-binding

Inhibition of bovine CA by 5-methyl-l,10-phenanthroline and aniline involves direct tertiary co-ordination to the zinc ion. With the latter reagent, however, H n.m.r. relaxation of metal-bound water is unchanged on aniline co-ordination suggesting either that a histidine ligand is replaced or that a fifth co-ordination site is available. By contrast, methanol binds at a hydrophobic region ca. 6 A from the metal site and shows non-competitive inhibition of p-nitrophenyl acetate hydrolysis activity. ... 

In contrast to 1, isomeric p-nitrophenyl nicotinate shows almost no catalysis. Thus, it is clear that substrate coordination to the metal ion complex plays the critical role for an enormous rate enhancement. The lipophilic ester (R = C5Hn) also undergoes a large rate enhancement indicating the importance of substrate binding into the micellar phase by hydrophobic interaction. A large rate enhancement can also be seen in lipophilic esters which lack the metal coordination site as given below with the enantioselective micellar reactions (Table 9, 10). 

In the following section, the role of the various types of complexes mentioned above will be discussed with regard to various mechanisms of interactions at biological interphases. It is clear that metal ions and hydrophilic complexes cannot distribute into the membrane lipid bilayer or cross it. The role of hydrophilic ligands has thus to be discussed in relation to binding of metals by biological ligands. In contrast, hydrophobic complexes may partition into the lipid bilayer of membranes (see below, Section 6). 

Phenol binds to the hydrophobic pocket it is a competitive inhibitor for CO2 hydration and mixed non-competitive inhibitor of HCOg dehydration reaction (192a,193). In contrast, 2-nitrophenol is shown to be uncompetitive with respect to CO2 hydration at high pH. 1,2,4-Triazole is a non-competitive inhibitor towards both CO2 hydration and HCO3 dehydration (194). In contrast, tetrazole as an inhibitor is uncompetitive for C02 hydration and competitive for HCO3 dehydration at neutral and alkaline pH (194). Different inhibitors showing metal coordination with native enzyme and that of the Co-variant are presented in Table V. 

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