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

NWIPB OpenIR

	QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a
	Wang, Jinhu ; Sheng, Xiang ; Zhao, Yi ; Liu, Yongjun ; Liu, Chengbu
	2012-05-01
发表期刊	BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS ; Zhu, ZH; Wang, XA; Li, YNA; Wang, G; Guo, H.QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a,BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(5):750-758
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.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/47058
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	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, Zhu, ZH; Wang, XA; Li, YNA; Wang, G; Guo, H.QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a,BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(5):750-758,2012.
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.
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 (2012).