Insights on the Origin of Catalysis on Glycine N-Methyltransferase from Computational Modeling.

ABSTRACT: The origin of enzyme catalysis remains a question of debate despite much intense study. We report a QM/MM theoretical study of the S_N2 methyl transfer reaction catalyzed by a glycine N-methyltransferase (GNMT) and three mutants to test whether recent experimental observations of rate-constant reductions and variations in inverse secondary α-³H kinetic isotope effects (KIEs) should be attributed to changes in the methyl donor-acceptor distance (DAD): Is catalysis due to a compression effect? Semiempirical (AM1) and DFT (M06-2X) methods were used to describe the QM subset of atoms, while OPLS-AA and TIP3P classical force fields were used for the protein and water molecules, respectively. The computed activation free energies and KIEs are in good agreement with experimen

SUBMITTER: Swiderek K 

PROVIDER: S-EPMC6613375 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature