Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease

Science. 1990 Aug 3;249(4968):527-33. doi: 10.1126/science.2200122.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Drug Design
  • Endopeptidases / metabolism*
  • Gene Products, pol / metabolism*
  • HIV Protease
  • HIV-1 / enzymology*
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Protease Inhibitors / pharmacology*
  • Protein Conformation
  • Sugar Alcohols / pharmacology*
  • Valine / analogs & derivatives*
  • Valine / pharmacology


  • Gene Products, pol
  • Protease Inhibitors
  • Sugar Alcohols
  • A 74704
  • Endopeptidases
  • HIV Protease
  • Valine