Skip to main content

Advertisement

SpringerLink
Log in

Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1

  • Article
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

The crystal structure of the protease of the human immunodeficiency virus type 1 (HIV-1), which releases structural proteins and enzymes from viral polyprotein products, has been determined to 3 Å resolution. Large regions of the protease dimer, including the active site, have structural homology to the family of microbial aspartyl proteases. The structure suggests a mechanism for the autoproteolytic release of protease and a role in the control of virus maturation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Weiss, A., Hollander, H. & Stobo, J. A. Rev. Med. 36, 545–562 (1985).

    Article  CAS  Google Scholar 

  2. Gallo, R. C. & Montagnier, L. Scient. Am. 259(4), 40–48 (1988).

    Article  Google Scholar 

  3. Dickson, C., Eisenman, R., Fan, H., Hunter, E. & Teich, N. in RNA Tumor Viruses 2nd edn (eds Weiss, R., Teich, N., Varmus, H. & Coffin, J.) 513–648 (Cold Spring Harbor Laboratory, New York, 1984).

    Google Scholar 

  4. Witte, O. N. & Baltimore, D. J. Virol. 26, 750–761 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Crawford, S. & Goff, S. P. J. Virol. 53, 899–907 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Katoh, I. et al. Virology 145, 280–292 (1985).

    Article  CAS  PubMed  Google Scholar 

  7. Farmerie, W. G. et al. Science 236, 305–308 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Darke, P. L. et al. Biochem. biophys. Res. Commun. 156, 297–303 (1988).

    Article  CAS  PubMed  Google Scholar 

  9. Toh, H., Ono, M., Saigo, K. & Miyata, T. Nature 315, 691 (1985).

    Article  ADS  CAS  Google Scholar 

  10. Seelmeier, S., Schmidt, H., Turk, V. & von der Helm, K. Proc. natn. Acad. Sci. U.S.A. 85, 6612–6616 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Hansen, J., Billich, S., Schulze, T., Sukrow, S. & Moelling, K. EMBO J. 7, 1785–1791 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Darke, P. L. et al. J. biol. Chem. 264, 2307–2312 (1989).

    CAS  PubMed  Google Scholar 

  13. Umezawa, H. et al. J. Antibiot. 23, 259–262 (1970).

    Article  CAS  Google Scholar 

  14. Kohl, N. E. et al. Proc. natn. Acad. Sci. U.S.A. 85, 4686–4690 (1988).

    Article  ADS  CAS  Google Scholar 

  15. Mous, J., Heimer, E. P. & Le Grice, S. F. J. J. Virol. 62, 1433–1436 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Debouck, C. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8903–8906 (1987).

    Article  ADS  CAS  Google Scholar 

  17. Graves, M. C., Lim, J. J., Heimer, E. P. & Kramer, R. A. Proc. natn. Acad. Sci. U.S.A. 85, 2449–2453 (1988).

    Article  ADS  CAS  Google Scholar 

  18. Nutt, R. F. et al. Proc. natn. Acad. Sci. U.S.A. 85, 7129–7133 (1988).

    Article  ADS  CAS  Google Scholar 

  19. Schneider, J. & Kent, S. B. H. Cell 54, 363–368 (1988).

    Article  CAS  PubMed  Google Scholar 

  20. Tang, J., James, M. N. G., Hsu, I. N., Jenkins, J. A. & Blundell, T. L. Nature 271, 618–621 (1978).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Subramanian, E. et al. Proc. natn. Acad. Sci. U.S.A. 74, 556–559 (1977).

    Article  ADS  CAS  Google Scholar 

  22. McKeever, B. M. et al. J. biol. Chem. 264, 1919–1921 (1989).

    CAS  PubMed  Google Scholar 

  23. Bernstein, F. C. et al. J. molec. Biol. 112, 535–542 (1977).

    Article  CAS  PubMed  Google Scholar 

  24. Suguna, K. et al. J. molec. Biol. 196, 877–900 (1987).

    Article  CAS  PubMed  Google Scholar 

  25. James, M. N. G. & Sielecki, A. J. molec. Biol. 163, 299–361 (1983).

    Article  CAS  PubMed  Google Scholar 

  26. Pearl, L. & Blundell, T. FEBS Lett. 174, 96–101 (1984).

    Article  CAS  PubMed  Google Scholar 

  27. Pearl, L. H. & Taylor, W. R. Nature 239, 351–354 (1987).

    Article  ADS  Google Scholar 

  28. Jacks, T. et al. Nature 331, 280–283 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Giam, C.-Z. & Boros, I. J. biol. Chem. 263, 14617–14620 (1988).

    CAS  PubMed  Google Scholar 

  30. Henderson, L. E., Krutzsch, H. C. & Oroszlan, S. Proc. natn. Acad. Sci. U.S.A. 80, 339–343 (1983).

    Article  ADS  CAS  Google Scholar 

  31. Mervis, R. J. et al. J. Virol. 62, 3993–4002 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Gonda, M. A. et al. Science 227, 173–177 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Suguna, K., Padlan, E. A., Smith, C. W., Carlson, W. D. & Davies, D. R. Proc. natn. Acad. Sci. U.S.A. 84, 7009–7013 (1987).

    Article  ADS  CAS  Google Scholar 

  34. James, M. N. G. & Sielecki, A. R. Biochemistry 24, 3701–3713 (1985).

    Article  CAS  PubMed  Google Scholar 

  35. Pearl, L. H. FEBS Lett. 214, 8–12 (1987).

    Article  CAS  PubMed  Google Scholar 

  36. Benn, S. et al. Science 230, 949–951 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  37. Howard, A. J. et al. J. appl. Crystallogr. 20, 383–387 (1987).

    Article  CAS  Google Scholar 

  38. Steigemann, W. thesis, Technische Universtät, München (1974).

  39. Jones, T. A. J. appl. Crystallogr. 11, 268–272 (1978).

    Article  CAS  Google Scholar 

  40. Sussman, J. L. Meth. Enzym. 115, 271–303 (1985).

    Article  CAS  PubMed  Google Scholar 

  41. Brünger, A. T., Kuriyan, J. & Karplus, M., Science 235, 458–460 (1987).

    Article  ADS  PubMed  Google Scholar 

  42. Hendrickson, W. A. Meth. Enzym. 115, 252–270 (1985).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biophysical Chemistry, Merck Sharp and Dohme Research Laboratories, PO Box 2000 (RY80M-203), Rahway, New Jersey, 07065, USA

    Manuel A. Navia, Paula M. D. Fitzgerald, Brian M. McKeever & James P. Springer

  2. Department of Molecular Biology, Merck Sharp and Dohme Research Laboratories, Sumneytown Pike (WP16-101), West Point, Pennsylvania, 19486, USA

    Chih-Tai Leu, Jill C. Heimbach, Wayne K. Herber, Irving S. Sigal & Paul L. Darke

Author notes

  1. Sadly, Dr Irving S. Sigal was killed in the destruction of Pan Am Flight 103 over Lockerbie, Scotland on 20 December 1988.

    • Irving S. Sigal
Authors
  1. Manuel A. Navia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paula M. D. Fitzgerald
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian M. McKeever
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chih-Tai Leu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jill C. Heimbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wayne K. Herber
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Irving S. Sigal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paul L. Darke
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. James P. Springer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Navia, M., Fitzgerald, P., McKeever, B. et al. Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature 337, 615–620 (1989). https://doi.org/10.1038/337615a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/337615a0

  • Springer Nature Limited

This article is cited by

Search

Navigation