Structural basis for chiral substrate recognition by two 2,3‐butanediol dehydrogenases

M. Otagiri,S. Ui,Yuhsuke Takusagawa,T. Ohtsuki,G. Kurisu,M. Kusunoki

Published 2010 in FEBS Letters

ABSTRACT

2,3‐Butanediol dehydrogenase (BDH) catalyzes the NAD‐dependent redox reaction between acetoin and 2,3‐butanediol. There are three types of homologous BDH, each stereospecific for both substrate and product. To establish how these homologous enzymes possess differential stereospecificities, we determined the crystal structure of l‐BDH with a bound inhibitor at 2.0 Å. Comparison with the inhibitor binding mode of meso‐BDH highlights the role of a hydrogen‐bond from a conserved Trp residue192. Site‐directed mutagenesis of three active site residues of meso‐BDH, including Trp190, which corresponds to Trp192 of l‐BDH, converted its stereospecificity to that of l‐BDH. This result confirms the importance of conserved residues in modifying the stereospecificity of homologous enzymes.

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