Identification of a small molecule nonpeptide active site β-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases
Identification of a small molecule nonpeptide active site β-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases
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DOI：
10.1021/jm049388p
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发表时间：
2004-12-02
影响因子：
7.3
通讯作者：
Wang, T
中科院分区：
文献类型：
--
作者：
Coburn, CA;Stachel, SJ;Wang, T
一种β -分泌酶的小分子非肽抑制剂已经被开发出来，它的结合已经通过酶抑制剂复合物的晶体学测定被确定。该分子在天冬氨酸蛋白酶抑制领域以前所未有的方式与催化天冬氨酸残基结合。此外，该复合物揭示了由抑制剂产生的迄今未知的S-3子口袋。这种结构在新型β -分泌酶抑制剂的设计中发挥了重要作用。
A small molecule nonpeptide inhibitor of beta-secretase has been developed, and its binding has been defined through crystallographic determination of the enzyme-inhibitor complex. The molecule is shown to bind to the catalytic aspartate residues in an unprecedented manner in the field of aspartyl protease inhibition. Additionally, the complex reveals a heretofore unknown S-3 subpocket that is created by the inhibitor. This structure has served an important role in the design of newer beta-secretase inhibitors.