发现可诱导活性位点构象变化的非共价二肽基肽酶IV抑制剂。
Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site.
作者信息
Sheehan Scott M, Mest Hans-Juergen, Watson Brian M, Klimkowski Valentine J, Timm David E, Cauvin Annick, Parsons Stephen H, Shi Qing, Canada Emily J, Wiley Michael R, Ruehter Gerd, Evers Britta, Petersen Soenke, Blaszczak Larry C, Pulley Shon R, Margolis Brandon J, Wishart Graham N, Renson Beatrice, Hankotius Dirk, Mohr Michael, Zechel Johann-Christian, Michael Kalbfleisch J, Dingess-Hammond Elizabeth A, Boelke Andre, Weichert Andreas G
机构信息
Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA.
出版信息
Bioorg Med Chem Lett. 2007 Mar 15;17(6):1765-8. doi: 10.1016/j.bmcl.2006.12.074. Epub 2006 Dec 24.
A series of non-covalent inhibitors of the serine protease dipeptidyl peptidase IV (DPP-IV) were found to adopt a U-shaped binding conformation in X-ray co-crystallization studies. Remarkably, Tyr547 undergoes a 70 degrees side-chain rotation to accommodate the inhibitor and allows access to a previously unexposed area of the protein backbone for hydrogen bonding.
在X射线共结晶研究中发现，一系列丝氨酸蛋白酶二肽基肽酶IV（DPP-IV）的非共价抑制剂呈现出U形结合构象。值得注意的是，酪氨酸547的侧链旋转70度以容纳抑制剂，并使得能够与蛋白质主链先前未暴露的区域形成氢键。
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