Effect of Ba2+ on the activity and structure of α-glucosidase: Inhibition kinetics and molecular dynamics simulation

被引：22

作者：

Li, Xuan ^{[1
]}

Lu, Zhi-Rong ^{[2
]}

Wang, Wei ^{[2
]}

Han, Xiu Ping

Yang, Jun-Mo ^{[3
]}

Park, Yong-Doo ^{[2
]}

Zhou, Hai-Meng ^{[2
]}

Sheng, Qing ^{[1
]}

Lee, Jinhyuk ^{[4
,5
]}

机构：

[1] Zhejiang Sci Tech Univ, Coll Life Sci, Hangzhou 310018, Zhejiang, Peoples R China

[2] Tsinghua Univ, Zhejiang Prov Key Lab Appl Enzymol, Yangtze Delta Reg Inst, Jiaxing 314006, Peoples R China

[3] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Dermatol, Seoul 135710, South Korea

[4] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr KOBIC, Taejon 305806, South Korea

[5] Univ Sci & Technol, Dept Bioinformat, Taejon 305350, South Korea

来源：

PROCESS BIOCHEMISTRY | 2015年 / 50卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

alpha-Glucosidase; Ba2+; Inhibition kinetics; Unfolding; Molecular dynamics; Docking simulation; METHANOL DEHYDROGENASE; ENZYME; K+; SUBSTRATE; SPECIFICITY; DERIVATIVES; ACTIVATION; MECHANISMS; XANTHONES; DOCKING;

D O I：

10.1016/j.procbio.2015.01.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

It is important to study enzyme inhibition of alpha-glucosidase (EC 3.2.1.20) due to its physiological role as well as clinical relevance. In the present study, we examined the effect of Ba2+ on alpha-glucosidase (EC 3.2.1.20) by integrating enzyme kinetics and computational simulations. The results showed that Ba2+ directly bound to this enzyme and induced inhibition through structural changes. Ba2+ inhibited alpha-glucosidase in a mixed-type reaction (K-i = 55.50 +/- 2.12 mM) and directly induced the regional unfolding of alpha-glucosidase, resulting in a slight hydrophobic exposure. The computational simulations via molecular dynamics showed that Ba2+ directly bound to the active site entrance on alpha-glucosidase resulting in structural changes in this enzyme. Thus, this study provides insights into the mechanism of Ba2+ ligand binding-induced inhibition and structural change in alpha-glucosidase to increase the current understanding of the toxicity of Ba2+ on the carbohydrate catabolic enzyme alpha-glucosidase. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：582 / 588

页数：7

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