Binding of kunitz and eglin c inhibitors to serine proteinases: thermodynamic, kinetic and molecular aspects

Abstract

Protein-protein recognition is not a simple process, but consists of a space-time series of events involving among other aspects: molecular flexibility; induced fit; entropy, enthalpy and free energy changes; solvent; as well as hydrophobic, van der Waals and electrostatic interactions. Since the reaction of serine proteinases with macromolecular inhibitors appears to be a good model for studying protein-protein interactions, thermodynamics and kinetics for BPTI and eglin c binding to human γ-thrombin, human leukocyte elastase, bovine β-trypsin, bovine α-chymotrypsin and/or subtilisin Carlsberg have been investigated and analyzed in the light of the available molecular models. Analysis of the data indicates that proteinase: inhibitor interactions follow multi-step processes involving various intermediates, until the system leads to the final adduct.