一种小分子非肽活性位点β-分泌酶抑制剂的鉴定，该抑制剂对天冬氨酸蛋白酶呈现非传统结合模式。
Identification of a small molecule nonpeptide active site beta-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases.
作者信息
Coburn Craig A, Stachel Shawn J, Li Yue-Ming, Rush Diane M, Steele Thomas G, Chen-Dodson Elizabeth, Holloway M Katharine, Xu Min, Huang Qian, Lai Ming-Tain, DiMuzio Jillian, Crouthamel Ming-Chih, Shi Xiao-Ping, Sardana Vinod, Chen Zhongguo, Munshi Sanjeev, Kuo Lawrence, Makara Gergely M, Annis D Allen, Tadikonda Praveen K, Nash Huw M, Vacca Joseph P, Wang Tong
机构信息
Department of Medicinal Chemistry, Merck Research Laoratories, West Point, PA 19486-0004, USA.
出版信息
J Med Chem. 2004 Dec 2;47(25):6117-9. doi: 10.1021/jm049388p.
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.
一种β-分泌酶的小分子非肽抑制剂已被研发出来，并且通过酶-抑制剂复合物的晶体学测定确定了其结合方式。在天冬氨酸蛋白酶抑制领域，该分子以一种前所未有的方式与催化天冬氨酸残基结合。此外，该复合物揭示了一个由抑制剂产生的此前未知的S(3)亚口袋。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。
Zotero 插件