Critical role of substrate conformational change in the proton transfer process catalyzed by 4-oxalocrotonate tautomerase.

ABSTRACT: 4-Oxalocrotonate tautomerase enzyme (4-OT) catalyzes the isomerization of 2-oxo-4-hexenedioate to 2-oxo-3-hexenedioate. The chemical process involves two proton transfers, one from a carbon of the substrate to the nitrogen of Pro1 and another from this nitrogen atom to a different carbon of the substrate. In this paper the isomerization has been studied using the combined quantum mechanical and molecular mechanical method with a dual-level treatment of the quantum subsystem employing the MPW1BK density functional as the higher level. Exploration of the potential energy surface shows that the process is stepwise, with a stable intermediate state corresponding to the deprotonated substrate and a protonated proline. The rate constant of the overall process has been evaluated using ensemble-av

SUBMITTER: Ruiz-Pernia JJ 

PROVIDER: S-EPMC2746755 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature