Mechanism of the Humicola insolens Cel7B E197S mutant catalyzed flavonoid glycosides synthesis: a QM/MM metadynamics simulation study

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	Mechanism of the Humicola insolens Cel7B E197S mutant catalyzed flavonoid glycosides synthesis: a QM/MM metadynamics simulation study
	Zhang, Yu; Yan, Shihai; Yao, Lishan
刊名	THEORETICAL CHEMISTRY ACCOUNTS
	2013-06-01
卷号	132 期号:6 页码:1-10
关键词	Glycosynthase Catalytic mechanism Free energy surface QM/MM metadynamics Molecular dynamics
中文摘要	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.
英文摘要	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.
学科主题	仿真与模拟
WOS标题词	Science & Technology ; Physical Sciences
类目[WOS]	Chemistry, Physical
研究领域[WOS]	Chemistry
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记录号	WOS:000320448400006
公开日期	2014-03-21
内容类型	期刊论文
源URL	[http://ir.qibebt.ac.cn:8080/handle/337004/1641]
专题	青岛生物能源与过程研究所_仿真模拟团队
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.