Mechanistic Insight into Enzymatic Glycosyl Transfer with Retention of Configuration through Analysis of Glycomimetic Inhibitors

被引:81
作者
Errey, James C. [1 ]
Lee, Seung Seo [1 ]
Gibson, Robert P. [2 ]
Fleites, Carlos Martinez [2 ]
Barry, Conor S. [1 ]
Jung, Pierre M. J. [3 ]
O'Sullivan, Anthony C. [3 ]
Davis, Benjamin G. [1 ]
Davies, Gideon J. [2 ]
机构
[1] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England
[2] Univ York, Dept Chem, York YO10 5YW, N Yorkshire, England
[3] Syngenta AG, CH-4332 Stein, Switzerland
基金
英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;
关键词
bisubstrate mimetic; enzymes; glycosyltransferases; internal return; trehaloses; ANTIBIOTIC VALIDAMYCINS; CRYSTAL-STRUCTURE; TREHALOSE; BIOSYNTHESIS; SOLVOLYSIS; COMPLEX; DONOR;
D O I
10.1002/anie.200905096
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
(Figure Presented) Structural "valid"-ation: The mechanism of enzyme-catalyzed glycosyl transfer with retention of anomeric configuration continues to baffle, a situation compounded by the lack of insightful 3-D structures of ternary enzyme complexes. Synthesis and multi-dimensional kinetic analysis of validoxylamine derivatives are used to access the 3-D structure of a ternary complex (see picture; U = uridyl) providing insight into the geometry and donor-acceptor interplay at the glycosyltransfer site. © 2010 Wiley-VCH Verlag GmbH &. Co. KGaA.
引用
收藏
页码:1234 / 1237
页数:4
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