SNAP output for PDB entry 3v4i [SNAP web server]

PDB-id

3v4i; SNAP-derived features in text and JSON formats; DNAproDB

Class

transferase-DNA

Method

X-ray (2.8 Å)

Summary

Crystal structure of hiv-1 reverse transcriptase (rt) with DNA and azttp

Reference

Das K, Martinez SE, Bauman JD, Arnold E (2012): "HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism." Nat.Struct.Mol.Biol., 19, 253-259. doi: 10.1038/nsmb.2223.

Abstract

Combinations of nucleoside and non-nucleoside inhibitors (NNRTIs) of HIV-1 reverse transcriptase (RT) are widely used in anti-AIDS therapies. Five NNRTIs, including nevirapine, are clinical drugs; however, the molecular mechanism of inhibition by NNRTIs is not clear. We determined the crystal structures of RT-DNA-nevirapine, RT-DNA, and RT-DNA-AZT-triphosphate complexes at 2.85-, 2.70- and 2.80-Å resolution, respectively. The RT-DNA complex in the crystal could bind nevirapine or AZT-triphosphate but not both. Binding of nevirapine led to opening of the NNRTI-binding pocket. The pocket formation caused shifting of the 3' end of the DNA primer by ~5.5 Å away from its polymerase active site position. Nucleic acid interactions with fingers and palm subdomains were reduced, the dNTP-binding pocket was distorted and the thumb opened up. The structures elucidate complementary roles of nucleoside and non-nucleoside inhibitors in inhibiting RT.