QM/MM Simulations for the Broken-Symmetry Catalytic Reaction Mechanism of Human Arginase I.

ABSTRACT: Human arginase I (HARGI) is a metalloprotein highly expressed in the liver cytosol and catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. Understanding the reaction mechanism would be highly helpful to design new inhibitor molecules for HARGI as it is a target for heart- and blood-related diseases. In this study, we explored the hydrolysis reaction mechanism of HARGI with antiferromagnetic and ferromagnetic coupling between two Mn(II) ions at the catalytic site by employing molecular dynamics simulations coupled with quantum mechanics and molecular mechanics (QM/MM). The spin states, high-spin ferromagnetic couple (S _Mn1 = 5/2, S _Mn2 = 5/2), low-spin ferromagnetic couple (S _Mn1 = 1/2, S _Mn2 = 1/2), hi

SUBMITTER: Mudedla SK 

PROVIDER: S-EPMC9475637 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature