On the Entropic and Hydrophobic Properties Involved in the Inhibitory Mechanism of Carboxypeptidase A by its Natural Inhibitor from Potato

Abstract

The inhibition of carboxypeptidase A (CPA) by its natural inhibitor from potato (PCI) has been widely analysed with theoretical and experimental methods. Several mutants of PCI have been obtained in order to study the physico-chemical properties related to the inhibition. Point mutations were performed in the C-tail of PCI given its fundamental role in the inhibition. The inhibition constant and the dissociation free energy of the complexes PCI-CPA was experimentally obtained for each mutant. The mutants were divided in two sets, those where the mutation was intrinsically affecting the conformation of the PCI C-tail, and those where the mutation affected the interaction between PCI and CPA. The crystallographic structure of PCI, as found in its complex with bovine carboxypeptidase A, was used to model the structure of these mutants.