Structural basis for chiral substrate recognition by two 2,3-butanediol dehydrogenases
Structural basis for chiral substrate recognition by two 2,3-butanediol dehydrogenases
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DOI：
10.1016/j.febslet.2009.11.068
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发表时间：
2010-01-04
期刊：
影响因子：
3.5
通讯作者：
Kusunoki, Masami
中科院分区：
文献类型：
--
作者：
Otagiri, Masato;Ui, Sadaharu;Kusunoki, Masami
2，3-丁二醇脱氢酶(2，3-丁二醇脱氢酶)催化NAD依赖的乙酰基和2，3-丁二醇之间的氧化还原反应。有三种类型的同源BDH，每一种对底物和产物都是立体特异的。为了确定这些同源酶如何具有不同的立体特异性，我们用2.0埃的结合抑制剂测定了L-BDH的晶体结构。与Meso-BDH的抑制剂结合模式相比，突出了保守的Trp残基(192)中的氢键的作用。对Meso-BDH3个活性位点残基进行定点突变，使其立体特异性转化为L-BDH型。这一结果证实了保守残基在修饰立体结构中的重要性。同源酶之城。(C)2009年欧洲生化学会联合会。爱思唯尔出版，版权所有。
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 angstrom. 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 stereospeci. city of homologous enzymes. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.