3V81

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

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history. 


Literature

HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism.

Das, K., Martinez, S.E., Bauman, J.D., Arnold, E.

(2012) Nat Struct Mol Biol 19: 253-259

  • DOI: https://doi.org/10.1038/nsmb.2223
  • Primary Citation of Related Structures:  
    3V4I, 3V6D, 3V81

  • 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.

    • Organizational Affiliation: 

    Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, USA.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 Reverse Transcriptase P66 subunit
A, C
556Human immunodeficiency virus type 1 BH10Mutation(s): 3 
Gene Names: gag-pol
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data)
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 Reverse Transcriptase P51 subunit
B, D
428Human immunodeficiency virus type 1 BH10Mutation(s): 1 
Gene Names: gag-pol
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data)
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains LengthOrganismImage
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')E [auth T],
G [auth E]		27N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 4
MoleculeChains LengthOrganismImage
DNA (5'-D(*A*CP*AP*GP*TP*CP*CP*CP*TP*GP*TP*TP*CP*GP*GP*(MRG)P*CP*GP*CP*CP*(ATM))-3')F [auth P],
H [auth F]		21N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NVP
Query on NVP
Download Ideal Coordinates CCD File 
I [auth A],
J [auth C]		11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B:2',3'-E][1,4]DIAZEPIN-6-ONE
C15 H14 N4 O
NQDJXKOVJZTUJA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ATM BindingDB:  3V81 Kd: min: 19, max: 2.49e+4 (nM) from 6 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.822α = 90
b = 132.052β = 100.84
c = 142.732γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-01-18
    Type: Initial release
  • Version 1.1: 2012-02-15
    Changes: Database references
  • Version 1.2: 2017-11-08
    Changes: Refinement description
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2024-11-20
    Changes: Structure summary