TY - JOUR
T1 - Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor
T2 - A platform for antiviral drug design
AU - Goldgur, Yehuda
AU - Craigie, Robert
AU - Cohen, Gerson H.
AU - Fujiwara, Tamio
AU - Yoshinaga, Tomokazu
AU - Fujishita, Toshio
AU - Sugimoto, Hirohiko
AU - Endo, Takeshi
AU - Murai, Hitoshi
AU - Davies, David R.
PY - 1999/11/9
Y1 - 1999/11/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=13044295993&partnerID=8YFLogxK
U2 - 10.1073/pnas.96.23.13040
DO - 10.1073/pnas.96.23.13040
M3 - Article
C2 - 10557269
AN - SCOPUS:13044295993
SN - 0027-8424
VL - 96
SP - 13040
EP - 13043
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -