Open AccessStructural Basis of HIV-1 Inhibition by Nucleotide-Competing Reverse Transcriptase Inhibitor INDOPY-1
Author(s) -
Francesc Xavier Ruiz,
Anthony Hoang,
Kalyan Das,
Eddy Arnold
Publication year - 2019
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.9b01289
Subject(s) - reverse transcriptase , chemistry , nucleotide , enzyme , dna , nucleoside , dna polymerase , nucleoside reverse transcriptase inhibitor , polymerase , human immunodeficiency virus (hiv) , reverse transcriptase inhibitor , nucleotidyltransferase , stereochemistry , binding site , virology , biochemistry , polymerase chain reaction , rna , gene , biology
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.