A mechanism of action for carboxypeptidase A

Proc Natl Acad Sci U S A. 1972 Oct;69(10):2970-4. doi: 10.1073/pnas.69.10.2970.

Abstract

In an attempt to gain a better understanding of the mechanism of action of carboxypeptidase A (EC 3.4.2.1), many kinetic studies have been undertaken using numerous substrates-both esters and peptides-that have exhibited substrate linearity, inhibition, activation, and sigmoid-shaped rate plots. Numerous interpretations of the kinetic data have been proposed, none of which are fully in accord both with kinetic data and x-ray crystallographic studies. Much of the kinetic data has been interpreted using multisite binding while the x-ray information seems to severely restrict these possibilities. We have examined the feasibility of a simple model with a single active site, without modifier sites, that allows only one substrate molecule to bind the enzyme at a time. A random-pathway model was identified that simultaneously accounts for the nonlinear kinetic data and meets the restrictions imposed by the x-ray crystallographic studies.

MeSH terms

  • Binding Sites
  • Carboxypeptidases*
  • Chemical Phenomena
  • Chemistry
  • Crystallography
  • Esters
  • Hydrolysis
  • Kinetics
  • Models, Chemical
  • Peptides
  • Protein Binding
  • Protein Conformation
  • Structure-Activity Relationship

Substances

  • Esters
  • Peptides
  • Carboxypeptidases