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. 1990 Nov;87(22):8805–8809. doi: 10.1073/pnas.87.22.8805

X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor.

A L Swain 1, M M Miller 1, J Green 1, D H Rich 1, J Schneider 1, S B Kent 1, A Wlodawer 1
PMCID: PMC55048  PMID: 2247451

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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