QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis

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	QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis
	Hou, Q. Q.1; Sheng, X.1; Wang, J. H.1; Liu, Y. J.1,2; Liu, C. B.1
	2012-02-01
发表期刊	BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
ISSN	1570-9639
卷号	1824 期号:2 页码:263-268
文章类型	Article
摘要	Limonene 1,2-epoxide hydrolase (LEH) is completely different from those of classic epoxide hydrolases (EHs) which catalyze the hydrolysis of epoxides to vicinal diols. A novel concerted general acid catalysis step involving the Asp101-Arg99-Asp132 triad is proposed to play an important role in the mechanism. Combined quantum-mechanical/molecular-mechanical (QM/MM) calculations gave activation barriers of 16.9 and 25.1 kcal/mol at the B3LYP/6-31G(d,p)//CHARMM level for nucleophilic attack on the more and less substituted epoxide carbons, respectively. Furthermore, the important roles of residues Arg99, Tyr53 and Asn55 on mutated LEH were evaluated by QM/MM-scanned energy mapping. These results may provide an explanation for site-directed mutagenesis. (C) 2011 Elsevier B.V. All rights reserved.; Limonene 1,2-epoxide hydrolase (LEH) is completely different from those of classic epoxide hydrolases (EHs) which catalyze the hydrolysis of epoxides to vicinal diols. A novel concerted general acid catalysis step involving the Asp101-Arg99-Asp132 triad is proposed to play an important role in the mechanism. Combined quantum-mechanical/molecular-mechanical (QM/MM) calculations gave activation barriers of 16.9 and 25.1 kcal/mol at the B3LYP/6-31G(d,p)//CHARMM level for nucleophilic attack on the more and less substituted epoxide carbons, respectively. Furthermore, the important roles of residues Arg99, Tyr53 and Asn55 on mutated LEH were evaluated by QM/MM-scanned energy mapping. These results may provide an explanation for site-directed mutagenesis. (C) 2011 Elsevier B.V. All rights reserved.
关键词	Qm/mm Hydrolases Epoxide Ring-opening Reaction Mechanism Mutation
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]	AGROBACTERIUM-RADIOBACTER AD1 ; EPOXIDE HYDROLASE ; CATALYTIC MECHANISM ; MOLECULAR-DYNAMICS ; LIMONENE-1,2-EPOXIDE HYDROLASE ; ACTIVE-SITE ; INTERMEDIATE ; TYROSINE ; PROGRAM ; MODELS
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS类目	Biochemistry & Molecular Biology ; Biophysics
WOS记录号	WOS:000299986300001
引用统计	被引频次：10[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/3724
专题	中国科学院西北高原生物研究所
作者单位	1.Shandong Univ, Key Lab Colloid & Interface Chem, Minist Educ, Sch Chem & Chem Engn, Jinan 250100, Shandong, Peoples R China 2.Chinese Acad Sci, Key Lab Adaptat & Evolut Plateau Biota, NW Inst Plateau Biol, Xining 810008, Qinghai, Peoples R China
推荐引用方式 GB/T 7714	Hou, Q. Q.,Sheng, X.,Wang, J. H.,et al. QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(2):263-268.
APA	Hou, Q. Q.,Sheng, X.,Wang, J. H.,Liu, Y. J.,&Liu, C. B..(2012).QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis.BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,1824(2),263-268.
MLA	Hou, Q. Q.,et al."QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis".BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1824.2(2012):263-268.

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