DOI: 10.1126/science.2548279. Conserved Folding in Retroviral Proteases: Crystal Structure of Synthetic HIV-1 Protease

Conserved Folding in Retroviral Proteases: Crystal Structure of Synthetic HIV-1 Protease

10.1126/science.2548279

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The rational design of drugs that can inhibit the action of viral proteases depends on obtaining accurate structures of these enzymes. The crystal structure of chemically synthesized HIV-1 protease has been determined at 2.8 angstrom resolution ( R factor of 0.184) with the use of a model based on the Rous sarcoma virus protease structure. In this enzymatically active protein, the cysteines were replaced by α-amino- n -butyric acid, a nongenetically coded amino acid. This structure, in which all 99 amino acids were located, differs in several important details from that reported previously by others. The interface between the identical subunits forming the active protease dimer is composed of four well-ordered β strands from both the amino and carboxyl termini and residues 86 to 94 have a helical conformation. The observed arrangement of the dimer interface suggests possible designs for dimerization inhibitors.

Bibliography

Wlodawer, A., Miller, M., JaskÃ³lski, M., Sathyanarayana, B. K., Baldwin, E., Weber, I. T., Selk, L. M., Clawson, L., Schneider, J., & Kent, S. B. H. (1989). Conserved Folding in Retroviral Proteases: Crystal Structure of Synthetic HIV-1 Protease. Science, 245(4918), 616â621.

Authors 10

Alexander Wlodawer (first)
Maria Miller (additional)
Mariusz Jaskólski (additional)
Bangalore K. Sathyanarayana (additional)
Eric Baldwin (additional)
Irene T. Weber (additional)
Linda M. Selk (additional)
Leigh Clawson (additional)
Jens Schneider (additional)
Stephen B. H. Kent (additional)

References 34 Referenced 986

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10.1126/science.2537531

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 1:21 p.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 12:49 p.m.)
Indexed	1 week, 1 day ago (Aug. 21, 2025, 1:55 p.m.)
Issued	36 years ago (Aug. 11, 1989)
Published	36 years ago (Aug. 11, 1989)
Published Print	36 years ago (Aug. 11, 1989)

Funders 0

None

BibTeX

@article{Wlodawer_1989, title={Conserved Folding in Retroviral Proteases: Crystal Structure of Synthetic HIV-1 Protease}, volume={245}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2548279}, DOI={10.1126/science.2548279}, number={4918}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Wlodawer, Alexander and Miller, Maria and Jaskólski, Mariusz and Sathyanarayana, Bangalore K. and Baldwin, Eric and Weber, Irene T. and Selk, Linda M. and Clawson, Leigh and Schneider, Jens and Kent, Stephen B. H.}, year={1989}, month=aug, pages={616–621} }

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