7HVP

X-RAY CRYSTALLOGRAPHIC STRUCTURE OF A COMPLEX BETWEEN A SYNTHETIC PROTEASE OF HUMAN IMMUNODEFICIENCY VIRUS 1 AND A SUBSTRATE-BASED HYDROXYETHYLAMINE INHIBITOR

Summary for 7HVP

• Entry DOI: 10.2210/pdb7hvp/pdb
• Related PRD ID: PRD_000228
• Descriptor: HIV-1 PROTEASE, INHIBITOR ACE-SER-LEU-ASN-PHE-PSI(CH(OH)-CH2N)-PRO-ILE VME (JG-365) (3 entities in total)
• Functional Keywords: acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03369
• Total number of polymer chains: 3
• Total formula weight: 22374.31

Authors

Swain, A.L.,Miller, M.M.,Green, J.,Rich, D.H.,Schneider, J.,Kent, S.B.H.,Wlodawer, A. (deposition date: 1990-09-13, release date: 1993-07-15, Last modification date: 2023-11-15)

Primary citation

Swain, A.L.,Miller, M.M.,Green, J.,Rich, D.H.,Schneider, J.,Kent, S.B.,Wlodawer, A.
X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor.
Proc.Natl.Acad.Sci.USA, 87:8805-8809, 1990

PubMed Abstract: The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-psi[CH(OH)CH2N]-Pro-Ile-Val-OMe; the Ki is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-A resolution by using restrained least squares with rms deviations in bond lengths of 0.02 A and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365.

PubMed: 2247451
DOI: 10.1073/pnas.87.22.8805

Experimental method

X-RAY DIFFRACTION (2.4 Å)