title: Structural basis for chiral substrate recognition by two 2,3-butanediol dehydrogenases.
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 A. Comparison with the inhibitor binding mode of meso-BDH highlights the role of a hydrogen-bond from a conserved Trp residue(192). Site-directed mutagenesis of three active site residues of meso-BDH, including Trp(190), which corresponds to Trp(192) 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.
authors: Laboratory of Environmental Molecular Biology, RIKEN, Tsurumi-ward, Kanagawa, Japan.
authors: Masato
authors: M
authors: Otagiri
authors: Sadaharu
authors: S
authors: Ui
authors: Yuhsuke
authors: Y
authors: Takusagawa
authors: Takashi
authors: T
authors: Ohtsuki
authors: Genji
authors: G
authors: Kurisu
authors: Masami
authors: M
authors: Kusunoki
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D001951:Brevibacterium / Q000201:enzymology*; D002072:Butylene Glycols / Q000737:chemistry*; D020134:Catalytic Domain / Q000235:genetics; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013379:Substrate Specificity; D014364:Tryptophan / Q000737:chemistry* / Q000235:genetics
chemical_list: D002072:Butylene Glycols; C026978:2,3-butylene glycol; D014364:Tryptophan; D000429:Alcohol Oxidoreductases; C019801:butanediol dehydrogenase