Mechanism of OMP decarboxylation in orotidine 5'-monophosphate decarboxylase.

ABSTRACT: Despite extensive experimental and theoretical studies, the detailed catalytic mechanism of orotidine 5'-monophosphate decarboxylase (ODCase) remains controversial. In particular simulation studies using high level quantum mechanics have failed to reproduce experimental activation free energy. One common feature of many previous simulations is that there is a water molecule in the vicinity of the leaving CO2 group whose presence was only observed in the inhibitor bound complex of ODCase/BMP. Various roles have even been proposed for this water molecule from the perspective of stabilizing the transition state and/or intermediate state. We hypothesize that this water molecule is not present in the active ODCase/OMP complex. Based on QM/MM minimum free energy path simulations with accurate de

SUBMITTER: Hu H 

PROVIDER: S-EPMC3651880 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature