Unknown

Dataset Information

0

Fluxionate Lewis acidity of the Zn2+ ion in carboxypeptidase A.


ABSTRACT: Competitive inhibition constants Ki for a series of phenol-ring-substituted derivatives of alpha-(2-hydroxyphenyl)benzenepropanoic acid have been ascertained by observing their influence on the catalytic hydrolysis of a peptide substrate by the zinc enzyme carboxypeptidase A. The pH-dependence of Ki shows that binding is maximal between two pKa values: one is that of the phenol group of the inhibitor, and the other uniformly has a value of 6, the pKa of a Zn(2+)-bound water molecule on the enzyme in the absence of substrate or inhibitor. This is the dependence expected if phenolate binds to the Zn2+ displacing its bound H2O/HO-. A log-log plot of the dissociation constants for the productive forms of inhibitor plus enzyme versus the acid dissociation constants of the phenolic residues in the inhibitors yields a straight line with a slope of +0.76. This number indicates that the active-site metal ion has special capacity for dispersing negative charge, such as builds up on the oxygen atom of a carboxamide group undergoing nucleophilic addition.

SUBMITTER: Mock WL 

PROVIDER: S-EPMC1132148 | biostudies-other | 1993 Jan

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC7818483 | biostudies-literature
| S-EPMC6899571 | biostudies-literature
| S-EPMC5952319 | biostudies-other
| S-EPMC7154672 | biostudies-literature
| S-EPMC8361710 | biostudies-literature
| S-EPMC9306523 | biostudies-literature
| S-EPMC8596774 | biostudies-literature
| S-EPMC9133034 | biostudies-literature
| S-EPMC6316537 | biostudies-literature
| S-EPMC4428610 | biostudies-literature