Mechanism of the Humicola insolens Cel7B E197S mutant catalyzed flavonoid glycosides synthesis: a QM/MM metadynamics simulation study | |
Zhang, Yu; Yan, Shihai; Yao, Lishan | |
2013-06-01 | |
发表期刊 | THEORETICAL CHEMISTRY ACCOUNTS |
卷号 | 132期号:6页码:1-10 |
摘要 | The reaction path of Humicola insolens Cel7B E197S catalyzed glycosylation of luteolin by a-lactosyl fluoride was investigated using QM/MM metadynamics simulations. The catalysis proceeds via a sequential mechanism. Firstly, a proton transfers from the glycosyl acceptor, luteolin, to the catalytic acid/base residue, E202. Secondly, the C1–F covalent bond of the glycosyl donor, a-lactosyl fluoride, is cleaved with the assistance of the hydroxyl group of S197, and the F anion captures the carboxylic proton of D199, while the conformation of the glycosyl ring at -1 subsite changes from a chair to a halfchair. Thirdly, a new glycosidic bond is formed between C1 of the lactosyl cation and O4 0 of the luteolin anion during which a 1,4B boat conformation comes into being for the subsite -1 glycosyl ring. The rate-limiting step is the C1–F bond cleavage with a barrier of *25.9 kcal/mol. The change of geometric parameters and hydrogen bonds in the active site along the reaction is analyzed, revealing the important role of residues S197, D199, and E202. ; The reaction path of Humicola insolens Cel7B E197S catalyzed glycosylation of luteolin by alpha-lactosyl fluoride was investigated using QM/MM metadynamics simulations. The catalysis proceeds via a sequential mechanism. Firstly, a proton transfers from the glycosyl acceptor, luteolin, to the catalytic acid/base residue, E202. Secondly, the C-1-F covalent bond of the glycosyl donor, a-lactosyl fluoride, is cleaved with the assistance of the hydroxyl group of S197, and the F anion captures the carboxylic proton of D199, while the conformation of the glycosyl ring at -1 subsite changes from a chair to a half-chair. Thirdly, a new glycosidic bond is formed between C-1 of the lactosyl cation and O-4(') of the luteolin anion during which a (1,4) B boat conformation comes into being for the subsite -1 glycosyl ring. The rate-limiting step is the C1-F bond cleavage with a barrier of similar to 25.9 kcal/mol. The change of geometric parameters and hydrogen bonds in the active site along the reaction is analyzed, revealing the important role of residues S197, D199, and E202. |
文章类型 | Article |
关键词 | Glycosynthase Catalytic Mechanism Free Energy Surface Qm/mm Metadynamics Molecular Dynamics |
学科领域 | 仿真与模拟 |
WOS标题词 | Science & Technology ; Physical Sciences |
DOI | 10.1007/s00214-013-1367-3 |
关键词[WOS] | AB-INITIO METADYNAMICS ; MOLECULAR-DYNAMICS ; OLIGOSACCHARIDE SYNTHESIS ; CRYSTAL-STRUCTURE ; FORCE-FIELD ; GLYCOSYNTHASES ; ENZYMES ; INTEGRATION ; HYDROLYSIS |
收录类别 | SCI |
语种 | 英语 |
WOS研究方向 | Chemistry |
WOS类目 | Chemistry, Physical |
WOS记录号 | WOS:000320448400006 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.qibebt.ac.cn/handle/337004/1641 |
专题 | 蛋白质设计研究组 |
作者单位 | Chinese Acad Sci, Key Lab Biofuels, Qingdao Inst Bioenergy & Bioproc, Qingdao 266061, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Yu,Yan, Shihai,Yao, Lishan. Mechanism of the Humicola insolens Cel7B E197S mutant catalyzed flavonoid glycosides synthesis: a QM/MM metadynamics simulation study[J]. THEORETICAL CHEMISTRY ACCOUNTS,2013,132(6):1-10. |
APA | Zhang, Yu,Yan, Shihai,&Yao, Lishan.(2013).Mechanism of the Humicola insolens Cel7B E197S mutant catalyzed flavonoid glycosides synthesis: a QM/MM metadynamics simulation study.THEORETICAL CHEMISTRY ACCOUNTS,132(6),1-10. |
MLA | Zhang, Yu,et al."Mechanism of the Humicola insolens Cel7B E197S mutant catalyzed flavonoid glycosides synthesis: a QM/MM metadynamics simulation study".THEORETICAL CHEMISTRY ACCOUNTS 132.6(2013):1-10. |
条目包含的文件 | 下载所有文件 | |||||
文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
Mechanism of the Hum(921KB) | 开放获取 | CC BY-NC-SA | 浏览 下载 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论