Modulation of the affinity of aspartic proteases by the mutated residues in active site models

Publisher Website
Google Scholar
Abstract
The active sites of 3 types of aspartic proteases are modeled, based on crystallographic coordinates of endothiapepsin and of a model of HIV‐1 protease. The enthalpies of deprotonation from neutral to mono‐anion and to dianion are calculated with semiempirical minimal neglect of differential overlap, hydrogen bonding corrected (MNDO/H). This quantum mechanical study of models for the active sites of pepsins, human renin and retroviral aspartic proteases demonstrates that the replacements ofThr‐218 from pepsins by Ala in human renin and of both Ser‐35 and Thr‐218 by alanines in retroviral proteases increases the proton affinity and modulates the charge distribution of those active sites compared to the pepsins.