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

Maria Miller*, Mariusz Jaskólski, J. K Mohana Rao, Jonathan Leis, Alexander Wlodawer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

Abstract

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 virions1-11. On the basis of the conserved Asp-Thr/Ser-Gly sequence at the putative protease active sites, and other biochemical evidence2,3,12-16, 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 protein17, 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 protease18. We have now determined the crystal structure of Rous sarcoma virus (RSV) protease at 3-Å resolution and find it is dimeric and has a structure similar to aspartic proteases19-22. 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.

Original languageEnglish (US)
Pages (from-to)576-579
Number of pages4
JournalNature
Volume337
Issue number6207
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • General

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