3V6D

Crystal structure of HIV-1 reverse transcriptase (RT) cross-linked with AZT-terminated DNA

Summary for 3V6D

• Entry DOI: 10.2210/pdb3v6d/pdb
• Related: 1RTD 1VRT 2ZD1 3JSM 3KLE 3KLF 3V4I 3V81
• Descriptor: HIV-1 REVERSE TRANSCRIPTASE P66 subunit, HIV-1 REVERSE TRANSCRIPTASE P51 subunit, DNA (5'-D(*AP*TP*GP*GP*AP*AP*GP*GP*CP*GP*CP*CP*CP*GP*AP*AP*CP*AP*GP*GP*GP*AP*CP*TP*GP*TP*G)-3'), ... (4 entities in total)
• Functional Keywords: hiv-1 reverse transcriptase, zidovudine, rt-dna complex, transferase-dna complex, drug resistance mutation, aids, dna recombination, dna-directed dna polymerase, rnase h, hydrolase, lipoprotein, magnesium, membrane, metal-binding, multifunctional enzyme, nucleotidyltransferase, rna-directed dna polymerase transferase, transferase/dna
• Biological source: Human immunodeficiency virus type 1 BH10 (HIV-1); More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03366 P03366
• Total number of polymer chains: 8
• Total formula weight: 257937.19

Authors

Das, K.,Martinez, S.E.,Arnold, E. (deposition date: 2011-12-19, release date: 2012-01-18, Last modification date: 2023-09-13)

Primary citation

Das, K.,Martinez, S.E.,Bauman, J.D.,Arnold, E.
HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism.
Nat.Struct.Mol.Biol., 19:253-259, 2012

PubMed 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.

PubMed: 22266819
DOI: 10.1038/nsmb.2223

Experimental method

X-RAY DIFFRACTION (2.7048 Å)