1T05

HIV-1 reverse transcriptase crosslinked to template-primer with tenofovir-diphosphate bound as the incoming nucleotide substrate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.253 

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This is version 1.4 of the entry. See complete history


Literature

Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir

Tuske, S.Sarafianos, S.G.Clark Jr., A.D.Ding, J.Naeger, L.K.White, K.L.Miller, M.D.Gibbs, C.S.Boyer, P.L.Clark, P.Wang, G.Gaffney, B.L.Jones, R.A.Jerina, D.M.Hughes, S.H.Arnold, E.

(2004) Nat Struct Mol Biol 11: 469-474

  • DOI: https://doi.org/10.1038/nsmb760
  • Primary Citation of Related Structures:  
    1T03, 1T05

  • PubMed Abstract: 

    Tenofovir, also known as PMPA, R-9-(2-(phosphonomethoxypropyl)adenine, is a nucleotide reverse transcriptase (RT) inhibitor. We have determined the crystal structures of two related complexes of HIV-1 RT with template primer and tenofovir: (i) a ternary complex at a resolution of 3.0 A of RT crosslinked to a dideoxy-terminated DNA with tenofovir-diphosphate bound as the incoming substrate; and (ii) a RT-DNA complex at a resolution of 3.1 A with tenofovir at the 3' primer terminus. The tenofovir nucleotide in the tenofovir-terminated structure seems to adopt multiple conformations. Some nucleoside reverse transcriptase inhibitors, including 3TC and AZT, have elements ('handles') that project beyond the corresponding elements on normal dNTPs (the 'substrate envelope'). HIV-1 RT resistance mechanisms to AZT and 3TC take advantage of these handles; tenofovir's structure lacks handles that could protrude through the substrate envelope to cause resistance.


  • Organizational Affiliation

    Center for Advanced Biotechnology and Medicine and Rutgers University Department of Chemistry and Chemical Biology, 679 Hoes Lane, Piscataway, New Jersey 08854-5638, USA.


Macromolecules

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
POL polyproteinC [auth A]558Human immunodeficiency virus 1Mutation(s): 2 
Gene Names: POL
EC: 2.7.7.49
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: 4
MoleculeChains Sequence LengthOrganismDetailsImage
POL polyproteinD [auth B]437Human immunodeficiency virus 1Mutation(s): 1 
Gene Names: POL
EC: 2.7.7.49
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04585 
Go to UniProtKB:  P04585
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04585
Sequence Annotations
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  • Reference Sequence
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Entity ID: 1
MoleculeChains LengthOrganismImage
oligonucleotide templateA [auth T]27N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
oligonucleotide primerB [auth P]21N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TNV
Query on TNV

Download Ideal Coordinates CCD File 
G [auth A][2-(6-AMINO-9H-PURIN-9-YL)-1-METHYLETHOXY]METHYL-TRIPHOSPHATE
C9 H16 N5 O10 P3
IACQCQDWSIQSRP-ZCFIWIBFSA-N
GOL
Query on GOL

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H [auth A],
I [auth A],
J [auth A],
K [auth B],
L [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.253 
  • Space Group: P 31 1 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 171.57α = 90
b = 171.57β = 90
c = 156.27γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-05-11
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-23
    Changes: Data collection, Refinement description