Crystal structure of meso-2,3-butanediol dehydrogenase in a complex with NAD(+) and inhibitor mercaptoethanol at 1.7 angstrom resolution for understanding of chiral substrate recognition mechanisms

The crystal structure of a ternary complex of meso-2,3-butanediol dehydroge nase with NAD(+) and a competitive inhibitor, mercaptoethanol, has been det ermined at 1.7 Angstrom resolution by means of molecular replacement and re fined to a final R-factor of 0.194. The overall structure is similar to tho se of the other short chain dehydrogenase/reductase enzymes. The NAD(+) bin ding site, and the positions of catalytic residues Ser139, Tyr152, and Lys1 56 are also conserved. The crystal structure revealed that mercaptoethanol bound specifically to meso-2,3-butanediol dehydrogenase. Two residues aroun d the active site, GLn140 and Gly183, forming hydrogen bonds with the inhib itor, are important but not sufficient for distinguishing stereoisomerism o f a chiral substrate.