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.
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Miller, M., Jaskólski, M., Rao, J. et al. Crystal structure of a retroviral protease proves relationship to aspartic protease family. Nature 337, 576–579 (1989). https://doi.org/10.1038/337576a0
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DOI: https://doi.org/10.1038/337576a0
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