Quantum chemical study on the deacylation step of human chymase

Human chymase (HC) is a family of serine proteases and changes angiotensin I (AngI) for angiotensin II (AngII). This production of AngII by HC is the bypass pathway of renin-angiotensin system and has higher production ability than that. In this study, the deacylation mechanism by human chymase was revealed through quantum chemical calculations. The model reaction system was solved using ab initio MO method with Hartree-Fock level. It was found that HC had two elementary reactions via tetrahedral intermediate and proton relay did not occur through this deacylation step. Further we compared the structural differences between HC and acetylcholinesterase, which suggested that the surroundings of catalytic triad decided whether proton relay occurs or not in an enzyme.