Structural basis for chiral substrate recognition by two 2,3-butanediol dehydrogenases |
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Authors: | Masato Otagiri Sadaharu Ui Yuhsuke Takusagawa Genji Kurisu Masami Kusunoki |
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Affiliation: | a Laboratory of Environmental Molecular Biology, RIKEN, 1-7-29 Suehiro-cho, Tsurumi-ward, Kanagawa 230-0045, Japan b Graduate School of Medicine and Engineering, University of Yamanashi, Takeda, Kofu 400-8511, Japan c Division of Structural Biology, Institute for Protein Research, Osaka University, Yamadaoka, Suita 565-0871, Japan |
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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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Keywords: | AC, acetoin BD, 2,3-butanediol BDH, butanediol dehydrogenase SDR, short-chain dehydrogenase/reductase family |
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