Design, Activity, and 2.8 Å Crystal Structure of a C 2 Symmetric Inhibitor Complexed to HIV-1 Protease
- 3 August 1990
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 249 (4968), 527-533
- https://doi.org/10.1126/science.2200122
Abstract
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.Keywords
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