Mechanistic implications of the cysteine-nicotinamide adduct in aldehyde dehydrogenase based on quantum mechanical/molecular mechanical simulations.

ABSTRACT: Recent computer simulations of the cysteine nucleophilic attack on propanal in human mitochondrial aldehyde dehydrogenase (ALDH2) yielded an unexpected result: the chemically reasonable formation of a dead-end cysteine-cofactor adduct when NAD+ was in the "hydride transfer" position. More recently, this adduct found independent crystallographic support in work on formyltetrahydrofolate dehydrogenase, work which further found evidence of the same adduct on re-examination of deposited electron densities of ALDH2. Although the experimental data showed that this adduct was reversible, several mechanistic questions arise from the fact that it forms at all. Here, we present results from further quantum mechanical/molecular mechanical (QM/MM) simulations toward understanding the mechanistic impli

SUBMITTER: Wymore T 

PROVIDER: S-EPMC2529467 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature