QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a

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	QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a
	Wang, Jinhu 1; Sheng, Xiang 1; Zhao, Yi 2; Liu, Yongjun 1,2; Liu, Chengbu 1
	2012-05-01
发表期刊	BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
ISSN	1570-9639
卷号	1824 期号:5 页码:750-758
文章类型	Article
摘要	Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a is an inverting enzyme. In this paper, the hydrolysis mechanism of p-nitro-phenyl alpha-D-glucopyranoside (pNP-Glc) catalyzed by BtGH97a was firstly studied by using quantum mechanical/molecular mechanical (QM/MM) approach. Two possible reaction pathways were considered. In the first pathway, a water molecule deprotonated by a nucleophilic base (here E439 or E508) attacks firstly on the anomeric carbon of pNP-Glc, then a proton from an acid residue (E532) attacks on the glycosidic oxygen to finish the hydrolysis reaction (named as nucleophilic attack-first pathway). In the second pathway, the proton from E532 attacks firstly on the glycosidic oxygen, then the water deprotonated by the nucleophilic base attacks on the anomeric carbon of pNP-Glc (named as proton attack-first pathway). Our calculation results indicate that the nucleophilic attack-first pathway is favorable in energy, in which the nucleophilic attack process is the rate-determining step with an energy barrier of 15.4 kcal/mol in the case of residue E508 as nucleophilic base. In this rate-determining step, the deprotonation of water and the attack on the anomeric carbon are concerted. In the proton attack-first pathway, the proton attack on the glycosidic oxygen is the rate-determining step, and the energy barrier is 24.1 kcal/mol. We conclude that the hydrolysis mechanism would follow nucleophilic attack-first pathway. (C) 2012 Elsevier B.V. All rights reserved.; Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a is an inverting enzyme. In this paper, the hydrolysis mechanism of p-nitro-phenyl alpha-D-glucopyranoside (pNP-Glc) catalyzed by BtGH97a was firstly studied by using quantum mechanical/molecular mechanical (QM/MM) approach. Two possible reaction pathways were considered. In the first pathway, a water molecule deprotonated by a nucleophilic base (here E439 or E508) attacks firstly on the anomeric carbon of pNP-Glc, then a proton from an acid residue (E532) attacks on the glycosidic oxygen to finish the hydrolysis reaction (named as nucleophilic attack-first pathway). In the second pathway, the proton from E532 attacks firstly on the glycosidic oxygen, then the water deprotonated by the nucleophilic base attacks on the anomeric carbon of pNP-Glc (named as proton attack-first pathway). Our calculation results indicate that the nucleophilic attack-first pathway is favorable in energy, in which the nucleophilic attack process is the rate-determining step with an energy barrier of 15.4 kcal/mol in the case of residue E508 as nucleophilic base. In this rate-determining step, the deprotonation of water and the attack on the anomeric carbon are concerted. In the proton attack-first pathway, the proton attack on the glycosidic oxygen is the rate-determining step, and the energy barrier is 24.1 kcal/mol. We conclude that the hydrolysis mechanism would follow nucleophilic attack-first pathway. (C) 2012 Elsevier B.V. All rights reserved.
关键词	Btgh97a Pnp-glc Qm/mm Reaction Mechanism
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]	MOLECULAR-DYNAMICS ; HYDROLYSIS ; SYMBIONT ; FAMILY ; OPTIMIZATION ; HYDROLASES ; ALGORITHM ; PROGRAM ; SEARCH ; ENZYME
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:000304077200006
引用统计	被引频次：3[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/363003/3674
专题	中国科学院西北高原生物研究所
作者单位	1.Shandong Univ, Sch Chem & Chem Engn, Key Lab Theoret & Computat Chem, Jinan 250100, Shandong, Peoples R China 2.Chinese Acad Sci, NW Inst Plateau Biol, Xining 810001, Peoples R China
推荐引用方式 GB/T 7714	Wang, Jinhu,Sheng, Xiang,Zhao, Yi,et al. QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(5):750-758.
APA	Wang, Jinhu,Sheng, Xiang,Zhao, Yi,Liu, Yongjun,&Liu, Chengbu.(2012).QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a.BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,1824(5),750-758.
MLA	Wang, Jinhu,et al."QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a".BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1824.5(2012):750-758.

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