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Molecular Modeling of the HIV-2 Protease

  • Alla Gustchina
  • Irene T. Weber
  • Alexander Wlodawer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)

Abstract

The principal pathogen of acquired immunodeficiency syndrome (AIDS) in the United States is human immunodeficiency virus type 1 (HIV-1), but the disease is sometimes caused by a second variant, HIV-2. These two viruses share a similar genomic organization, indicating common evolutionary origin, but differ significantly in terms of nucleotide and amino-acid sequence, with no more than 60% overall amino-acid identity. Elucidation of the structures of virally-encoded enzymes offers an opportunity for rational drug design and has been pursued by many groups. The structure of only one enzyme encoded by HIV-1, that of the aspartyl protease (PR), is currently known (Navia et al., 1989; Wlodawer et al., 1989). This enzyme is essential for viral maturation, and is the target of choice for designing new therapeutic agents.

Keywords

Aspartic Protease Renin Inhibitor Aspartyl Protease Rational Drug Design Common Evolutionary Origin 
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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References

  1. Gustchina, A. & Weber, I. T., 1990. FEBS Lett. 269: 269–272.PubMedCrossRefGoogle Scholar
  2. Miller, M., Schneider, J., Sathyanarayana, B. K., Toth, M. V., Marshall, G. R., Clawson, L., Selk, L., Kent, S. B. H. & Wlodawer, A., 1989, Science 246: 1149–1152.PubMedCrossRefGoogle Scholar
  3. Navia, M. A., Fitzgerald, P. M. D., McKeever, B. M., Leu, C., Heimbach, J. C., Herber, W. K., Sigal, I. S., Darke, P. L. & Springer, J. P., 1989, Nature (London) 337: 615–620.CrossRefGoogle Scholar
  4. Richards, A. D., Roberts, R., Dunn, B. M., Graves, M. C. & Kay, J., 1989, FEBS Lett. 247: 113–117.PubMedCrossRefGoogle Scholar
  5. Richards, A. D., Broadhurst, A. V., Ritchie, A. J., Dunn, B. M. & Kay, J., 1990, FEBS Lett. 253: 214–216.CrossRefGoogle Scholar
  6. Swain, A. L., Miller, M., Green, J., Rich, D. H., Schneider, J., Kent, S. B. H. & Wlodawer, A., 1990, Proc. Natl. Acad. Sci. U.S.A. 87: 8805–8809.PubMedCrossRefGoogle Scholar
  7. Wlodawer, A., Miller, M., Jaskólski, M., Sathyanarayana, B. K., Baldwin, E., Weber, I. T., Selk, L. M., Clawson, L., Schneider, J. & Kent, S. B. H., 1989, Science 245: 616–621.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Alla Gustchina
    • 2
  • Irene T. Weber
    • 1
  • Alexander Wlodawer
    • 1
  1. 1.Crystallography LaboratoryNCI-Frederick Cancer Research and Development Center, ABL-Basic Research ProgramFrederickUSA
  2. 2.V.A. Engelhardt Institute of Molecular BiologyAcademy of Sciences of the USSRMoscowUSSR

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