王静云

个人信息Personal Information

教授

博士生导师

硕士生导师

性别:女

毕业院校:大连理工大学

学位:博士

所在单位:生物工程学院

学科:生物化工. 生物工程与技术. 药物工程

办公地点:生物楼512

联系方式:wangjingyun67@dlut.edu.cn

电子邮箱:wangjingyun67@dlut.edu.cn

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Rational design of Meso-2,3-butanediol dehydrogenase by molecular dynamics simulation and experimental evaluations

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论文类型:期刊论文

发表时间:2017-10-01

发表刊物:FEBS LETTERS

收录刊物:Scopus、SCIE、PubMed

卷号:591

期号:20

页面范围:3402-3413

ISSN号:1873-3468

关键字:meso-2; 3-butanediol dehydrogenase; rational design; short-chain dehydrogenase/reductase

摘要:Meso-2,3-butanediol dehydrogenase (meso-2,3-BDH) catalyzes NAD(+)-dependent conversion of meso-2,3-butanediol to acetoin, a crucial external energy storage molecule in fermentive bacteria. In this study, the active tunnel of meso-2,3-BDH was identified. The two short helixes positioned away from the 4-helix possibly expose the hydrophobic ligand-binding cavity, gating the exit of product and cofactor from the activity pocket. Further MM/GBSA-binding free energy analysis shows that Phe212 and Asn146 function as the key product-release sites. Site-directed mutagenesis experiments targeted to the sites show that the k(cat) of Phe212Tyr is enhanced up to (4-8)-fold. The original activity of Asn146Gln is retained, but the activity of Asn146Ala mutation is lost. These results could provide helpful guidance on rational design of short-chain dehydrogenases/reductases.