3V81

Crystal structure of HIV-1 reverse transcriptase (RT) with DNA and the nonnucleoside inhibitor nevirapine

Summary for 3V81

• Entry DOI: 10.2210/pdb3v81/pdb
• Related: 1RTD 1VRT 2ZD1 3JSM 3KLE 3KLF 3V4I 3V6D
• 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'), ... (5 entities in total)
• Functional Keywords: p51/p66, hetero dimer, nnrti, nonnucleoside inhibitor, aids, dna, recombination, rna-directed dna polymerase, viramune, dna polymerase, endonuclease, hydrolase, multifunctional enzyme, transferase, transferase-dna complex, azt, zidovudine, 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: 258469.78

Authors

Das, K.,Martinez, S.E.,Arnold, E. (deposition date: 2011-12-22, release date: 2012-01-18, Last modification date: 2024-11-20)

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 (2.8503 Å)