THE CONTRIBUTION OF ELECTROSTATIC AND VAN-DER-WAALS INTERACTIONS TO THE STEREOSPECIFICITY OF THE REACTION CATALYZED BY LACTATE-DEHYDROGENASE

Continuum electrostatic calculations in conjunction with molecular dyn amics simulations have been used to investigate the source of the ster eospecificity in the hydride transfer reaction catalyzed by lactate de hydrogenase (LDH). These studies show that favorable electrostatic int eractions between the carboxamide group of the reduced nicotinamide ad enine dinucleotide coenzyme and protein residues of the active site of LDH can account for much if not ail of the stereospecificity of the L DH-catalyzed reaction, with A-side hydride transfer more than 10(7) ti mes greater than B-side transfer. Unfavorable steric interactions with in the binding complex for B-side transfer are not found.