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Substrate Specificity of the Human (Type 1) and Simian Immunodeficiency Virus Proteases

  • Christine Debouck
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)

Abstract

All retroviruses have a small (ca. 10 kilobases) RNA genome that contains three major open reading frames typically organized in the order 5′-LTR-gag-pol-env-LTR-3′ The retroviral genome also encodes a protease of the aspartyl class that is responsible for the processing of the gag and gag-pol polyprotein precursors, both primary products of translation (see Dickson et al., 1984 for a review). Because they are essential for viral maturation and infectivity (Crawford & Goff, 1985; Katoh et al., 1985; Kohl et al., 1988; Peng et al., 1989), retroviral proteases have been the subject of intense investigation, particularly as a therapeutic target for the treatment of HIV infections (see Davies, 1990; Debouck & Metcalf, 1990; Hellen et al., 1989; Kay & Dunn, 1990, for reviews). In this context, the design of specific inhibitors of retroviral proteases requires the characterization of the mechanism of action and the substrate preferences of these enzymes. We discuss here a genetic approach towards understanding the substrate recognition by the HIV-1 protease and its closely related congener from the simian immunodeficiency virus, the SIVMAC protease.

Keywords

Human Immunodeficiency Virus Human Immunodeficiency Virus Type Cleavage Site Simian Immunodeficiency Virus Human Immunodeficiency Virus Protease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Christine Debouck
    • 1
  1. 1.Department of Molecular GeneticsSmithKline Beecham PharmaceuticalsKing of PrussiaUSA

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