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Science 3 August 1990:
Vol. 249. no. 4968, pp. 527 - 533
DOI: 10.1126/science.2200122
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Articles
Science, Vol 249, Issue 4968, 527-533
Copyright © 1990 by American Association for the Advancement of Science
Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease
J Erickson,
DJ Neidhart,
J VanDrie,
DJ Kempf,
XC Wang,
DW Norbeck,
JJ Plattner,
JW Rittenhouse,
M Turon,
N Wideburg,
and
al. et
Department of Computer-Assisted Molecular Design, Abbott Laboratories, Abbott Park, IL 60064.
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.
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