Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease
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 alpha-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.
Additional Information
© 1989 American Association for the Advancement of Science. 26 May 1989; Accepted 10 July 1989. We thank the Advanced Scientific Computing Laboratory, FCRF, for computer time on their CRAY X-MP. Sponsored in part by the National Cancer Institute, DHHS, under contract N01-CO-74101 with BRI, and in part by funds from the NSF Biological Instrumentation Division to S.B.H.K.Additional details
- Eprint ID
- 54183
- Resolver ID
- CaltechAUTHORS:20150128-103636013
- N01-CO-74101
- National Cancer Institute
- Department of Health and Human Services (DHHS)
- NSF
- Created
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2015-01-28Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field