DESIGN, ACTIVITY, AND 2.8 A CRYSTAL-STRUCTURE OF A C2 SYMMETRICAL INHIBITOR COMPLEXED TO HIV-1 PROTEASE
DESIGN, ACTIVITY, AND 2.8 A CRYSTAL-STRUCTURE OF A C2 SYMMETRICAL INHIBITOR COMPLEXED TO HIV-1 PROTEASE
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DOI：
10.1126/science.2200122
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发表时间：
1990-08-03
期刊：
影响因子：
56.9
通讯作者：
KNIGGE, M
中科院分区：
文献类型：
--
作者：
ERICKSON, J;NEIDHART, DJ;KNIGGE, M
基于酶活性位点的三维对称性，设计了一种人类免疫缺陷病毒1型（HIV-1）蛋白酶的二重（C2）对称抑制剂。这种对称分子在体外可抑制蛋白酶活性和急性 HIV-1 感染，其抗 HIV-1 蛋白酶的效力比相关酶强至少 10,000 倍，并且似乎对降解酶稳定。抑制剂-酶复合物的 2.8 埃晶体结构表明抑制剂以高度对称的方式与酶结合。
A two-fold (C2) symmetric inhibitor of the protease of human immunodeficiency virus type-1 (HIV-1) has been designed on the basis of the three-dimensional symmetry of the enzyme active site. The symmetric molecule inhibited both protease activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against HIV-1 protease than against related enzymes, and appeared to be stable to degradative enzymes. The 2.8 angstrom crystal structure of the inhibitor-enzyme complex demonstrated that the inhibitor binds to the enzyme in a highly symmetric fashion.