Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: A platform for antiviral drug design

Yehuda Goldgur, Robert Craigie, Gerson H. Cohen, Tamio Fujiwara, Tomokazu Yoshinaga, Toshio Fujishita, Hirohiko Sugimoto, Takeshi Endo, Hitoshi Murai, David R. Davies

Research output: Contribution to journalArticlepeer-review

522 Scopus citations

Abstract

HIV integrase, the enzyme that inserts the viral DNA into the host chromosome, has no mammalian counterpart, making it an attractive target for antiviral drug design. As one of the three enzymes produced by HIV, it can be expected that inhibitors of this enzyme will complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. We have determined the structure of a complex of the HIV-1 integrase core domain with a novel inhibitor, 5CITEP, 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2 H-tetrazol-5-yl)- propenone, to 2.1-Å resolution. The inhibitor binds centrally in the active site of the integrase and makes a number of close contacts with the protein. Only minor changes in the protein accompany inhibitor binding. This inhibitor complex will provide a platform for structure-based design of an additional class of inhibitors for antiviral therapy.

Original languageEnglish
Pages (from-to)13040-13043
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number23
DOIs
StatePublished - 9 Nov 1999
Externally publishedYes

ASJC Scopus subject areas

  • General

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