Abstract
HIV-1 reverse transcriptase (RT) is an essential enzyme, targeting half of approved anti-AIDS drugs. While nucleoside RT inhibitors (NRTIs) are DNA chain terminators, the nucleotide-competing RT inhibitor (NcRTI) INDOPY-1 blocks dNTP binding to RT. Lack of structural information hindered INDOPY-1 improvement. Here we report the HIV-1 RT/DNA/INDOPY-1 crystal structure, revealing a unique mode of inhibitor binding at the polymerase active site without involving catalytic metal ions. The structure may enable new strategies for developing NcRTIs.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
HIV Reverse Transcriptase / antagonists & inhibitors*
-
HIV Reverse Transcriptase / chemistry
-
HIV-1 / drug effects*
-
HIV-1 / enzymology*
-
Indoles / chemistry*
-
Indoles / pharmacology*
-
Models, Molecular
-
Nitriles / chemistry*
-
Nitriles / pharmacology*
-
Protein Conformation
-
Pyridones / chemistry*
-
Pyridones / pharmacology*
-
Reverse Transcriptase Inhibitors / chemistry*
-
Reverse Transcriptase Inhibitors / pharmacology*
Substances
-
5-methyl-1-(4-nitrophenyl)-2-oxo-2,5-dihydro-1H-pyrido(3,2-b)indole-3-carbonitrile
-
Indoles
-
Nitriles
-
Pyridones
-
Reverse Transcriptase Inhibitors
-
reverse transcriptase, Human immunodeficiency virus 1
-
HIV Reverse Transcriptase