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

被引:468
作者
Goldgur, Y
Craigie, R
Cohen, GH
Fujiwara, T
Yoshinaga, T
Fujishita, T
Sugimoto, H
Endo, T
Murai, H
Davies, DR
机构
[1] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA
[2] Shionogi & Co Ltd, Discovery Res Labs, Fukushima Ku, Osaka 5530002, Japan
关键词
D O I
10.1073/pnas.96.23.13040
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-(2H-tetrazole-5-yl)-pro-penone, to 2.1-Angstrom 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.
引用
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页码:13040 / 13043
页数:4
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