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

NWIPB OpenIR

	QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis
	Hou, Q. Q. ; Sheng, X. ; Wang, J. H. ; Liu, Y. J. ; Liu, C. B.
	2012-02-01
发表期刊	BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS ; Fang, HJ; Cheng, SL; Yu, GR; Zheng, JJ; Zhang, PL; Xu, MJ; Li, YN; Yang, XM.QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis,BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(2):263-268
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.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/36904
专题	中国科学院西北高原生物研究所
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, Fang, HJ; Cheng, SL; Yu, GR; Zheng, JJ; Zhang, PL; Xu, MJ; Li, YN; Yang, XM.QM/MM study of the mechanism of enzymatic limonene 1,2-epoxide hydrolysis,BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(2):263-268,2012.
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.
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 (2012).