基于枯草芽孢杆菌中一种NAD⁺/Mn²⁺依赖性磷酸-α-葡萄糖苷酶的结构的新型糖苷水解催化机制

Novel catalytic mechanism of glycoside hydrolysis based on the structure of an NAD+/Mn2+ -dependent phospho-alpha-glucosidase from Bacillus subtilis.

作者信息

Rajan Shyamala S, Yang Xiaojing, Collart Frank, Yip Vivian L Y, Withers Stephen G, Varrot Annabelle, Thompson John, Davies Gideon J, Anderson Wayne F

机构信息

Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

出版信息

Structure. 2004 Sep;12(9):1619-29. doi: 10.1016/j.str.2004.06.020.

DOI:10.1016/j.str.2004.06.020

PMID:15341727

Abstract

GlvA, a 6-phospho-alpha-glucosidase from Bacillus subtilis, catalyzes the hydrolysis of maltose-6'-phosphate and belongs to glycoside hydrolase family GH4. GH4 enzymes are unique in their requirement for NAD(H) and a divalent metal for activity. We have determined the crystal structure of GlvA in complex with its ligands to 2.05 A resolution. Analyses of the active site architecture, in conjunction with mechanistic studies and precedent from the nucleotide diphosphate hexose dehydratases and other systems, suggest a novel mechanism of glycoside hydrolysis by GlvA that involves both the NAD(H) and the metal.

摘要

GlvA是一种来自枯草芽孢杆菌的6-磷酸-α-葡萄糖苷酶，催化6'-磷酸麦芽糖的水解，属于糖苷水解酶家族GH4。GH4酶的独特之处在于其活性需要NAD(H)和二价金属。我们已经确定了与配体结合的GlvA的晶体结构，分辨率为2.05埃。结合机制研究以及核苷酸二磷酸己糖脱水酶和其他系统的先例，对活性位点结构的分析表明，GlvA的糖苷水解新机制涉及NAD(H)和金属。