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

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Oct 12

PMID 31603676

Citations 11

Authors

F Xavier Ruiz

Anthony Hoang

Kalyan Das

Eddy Arnold

Affiliations

Soon will be listed here.

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.

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