Mechanism of the Glycosylation Step Catalyzed by Human α-Galactosidase: A QM/MM Metadynamics Study

被引：14

作者：

Pan, Xiao-Liang ^{[1
]}

Liu, Wei ^{[1
]}

Liu, Jing-Yao ^{[1
]}

机构：

[1] Jilin Univ, Inst Theoret Chem, State Key Lab Theoret & Computat Chem, Changchun 130023, Peoples R China

来源：

JOURNAL OF PHYSICAL CHEMISTRY B | 2013年 / 117卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CELLULOSE HYDROLYSIS; CELLOBIOHYDROLASE I; MOLECULAR-MECHANISM; FABRY LYMPHOBLASTS; FORCE-FIELD; SUBSTRATE; DYNAMICS; DISEASE; INHIBITORS; DISPERSION;

D O I：

10.1021/jp308747c

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

The enzyme alpha-galactosidase (alpha-GAL), a member of glycoside hydrolase family 27, catalyzes the removal of a nonreducing terminal alpha-galactose residue from polysaccharides, glycolipids, and glycopeptides. alpha-GAL is believed to have the double displacement retaining reaction mechanism. In this work, the glycosylation step catalyzed by human alpha-GAL was computationally simulated with quantum mechanics/molecular mechanics metadynamics. Our simulations show that the overall catalytic mechanism follows a D-N*A(N)-like mechanism, and the transition state has a oxocarbenium ion like character with a partially formed double bond between the ring oxygen and C5' carbon atoms. In addition, the galactosyl ring of the substrate follows a conformational itinerary of C-4(1) -> [E-3/H-4(3)](double dagger) -> S-1(3) along the reaction coordinate.

引用

页码：484 / 489

页数：6

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