Fragment screening of inhibitors for MIF tautomerase reveals a cryptic surface binding site
Fragment screening of inhibitors for MIF tautomerase reveals a cryptic surface binding site
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DOI：
10.1016/j.bmcl.2010.02.009
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发表时间：
2010-03-15
影响因子：
2.7
通讯作者：
Li, Yi
中科院分区：
文献类型：
--
作者：
McLean, Larry R.;Zhang, Ying;Li, Yi
在片段筛选活动的过程中，通过计算机对接，然后通过X射线晶体学，证明了迁移抑制因子（MIF）抑制剂的一种新的结合位点。该位点是通过Tyr-36侧链的旋转形成的，以揭示MIF中的疏水性表面结合位点，并被芳族侧链残基包围。两个小的抑制剂，结合到这个网站和喹啉酮抑制剂，跨越典型的深口袋附近的Pro-1和新的表面结合位点的晶体结构，已经解决。这些结果为基于结构的MIF抑制剂设计提供了新的机会。(C)2010爱思唯尔有限公司保留所有权利。
In the course of a fragment screening campaign by in silico docking followed by X-ray crystallography, a novel binding site for migration inhibitory factor (MIF) inhibitors was demonstrated. The site is formed by rotation of the side-chain of Tyr-36 to reveal a surface binding site in MIF that is hydrophobic and surrounded by aromatic side-chain residues. The crystal structures of two small inhibitors that bind to this site and of a quinolinone inhibitor, that spans the canonical deep pocket near Pro-1 and the new surface binding site, have been solved. These results suggest new opportunities for structure-based design of MIF inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.