The structural basis of glycosidase inhibition by five-membered iminocyclitols:: The clan a glycoside hydrolase endoglycoceramidase as a model system

被引:36
作者
Caines, Matthew E. C.
Hancock, Susan M.
Tarling, Chris A.
Wrodnigg, Tanja M.
Stick, Robert V.
Stuetz, Arnold E.
Vasella, Andrea
Withers, Stephen G.
Strynadka, Natalie C. J.
机构
[1] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z3, Canada
[3] Graz Univ Technol, Inst Organ Chem, A-8010 Graz, Austria
[4] Univ Western Australia, Sch Biomed Biomol & Chem Sci, Crawley, WA 6009, Australia
[5] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland
关键词
carbohydrates; drug design; glycosidases; iminocyclitols; inhibitors;
D O I
10.1002/anie.200700268
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Fitting five into six: The crystal structure of a glycosidase-bound, flve-membered iminocyclitol inhibitor was determined (see picture), and its binding interactions were compared to those of the classical six-membered iminocyclitol inhibitors isofagomine and glucoimidazole and of the glycosyl-enzyme intermediate. This information may be used to develop more potent and specific therapeutically useful glycosidase inhibitors. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
引用
收藏
页码:4474 / 4476
页数:3
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