Structural Basis of HIV-1 Inhibition by Nucleotide-Competing Reverse Transcriptase Inhibitor INDOPY-1

F. Xavier Ruiz, Anthony Hoang, Kalyan Das, Eddy Arnold

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9996-10002
Number of pages7
JournalJournal of medicinal chemistry
Volume62
Issue number21
DOIs
StatePublished - Nov 14 2019

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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