Crystal structure of a retroviral protease proves relationship to aspartic protease family

Nature. 1989 Feb 9;337(6207):576-9. doi: 10.1038/337576a0.


Retroviral gag, pol and env gene products are translated as precursor polyproteins, which are cleaved by virus-encoded proteases to produce the mature proteins found in virions. On the basis of the conserved Asp-Thr/Ser-Gly sequence at the putative protease active sites, and other biochemical evidence, retroviral proteases have been predicted to be in the family of pepsin-like aspartic proteases. It has been suggested that aspartic proteases evolved from a smaller, dimeric ancestral protein, and a recent model of the human immunodeficiency virus (HIV) protease postulated that a symmetric dimer of this enzyme is equivalent to a pepsin-like aspartic protease. We have now determined the crystal structure of Rous sarcoma virus (RSV) protease at 3-A resolution and find it is dimeric and has a structure similar to aspartic proteases. This structure should provide a useful basis for the modelling of the structures of other retroviral proteases, such as that of HIV, and also for the rational design of protease inhibitors as potential antiviral drugs.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Aspartic Acid Endopeptidases
  • Avian Sarcoma Viruses* / genetics
  • Crystallography*
  • Endopeptidases* / genetics
  • Endopeptidases* / isolation & purification
  • Models, Molecular
  • Protein Conformation
  • Sequence Homology, Nucleic Acid
  • Structure-Activity Relationship


  • Endopeptidases
  • Aspartic Acid Endopeptidases