6BSI

Structure of HIV-1 RT complexed with an RNA/DNA hybrid containing the polypurine-tract sequence


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.25 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.195 

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This is version 1.4 of the entry. See complete history


Literature

Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid.

Tian, L.Kim, M.S.Li, H.Wang, J.Yang, W.

(2018) Proc Natl Acad Sci U S A 115: 507-512

  • DOI: https://doi.org/10.1073/pnas.1719746115
  • Primary Citation of Related Structures:  
    6BSG, 6BSH, 6BSI, 6BSJ

  • PubMed Abstract: 

    HIV-1 reverse transcriptase (RT) contains both DNA polymerase and RNase H activities to convert the viral genomic RNA to dsDNA in infected host cells. Here we report the 2.65-Å resolution structure of HIV-1 RT engaging in cleaving RNA in an RNA/DNA hybrid. A preferred substrate sequence is absolutely required to enable the RNA/DNA hybrid to adopt the distorted conformation needed to interact properly with the RNase H active site in RT. Substituting two nucleotides 4 bp upstream from the cleavage site results in scissile-phosphate displacement by 4 Å. We also have determined the structure of HIV-1 RT complexed with an RNase H-resistant polypurine tract sequence, which adopts a rigid structure and is accommodated outside of the nuclease active site. Based on this newly gained structural information and a virtual drug screen, we have identified an inhibitor specific for the viral RNase H but not for its cellular homologs.


  • Organizational Affiliation

    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
REVERSE TRANSCRIPTASE P66 SUBUNIT558Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: pol
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: 2
MoleculeChains Sequence LengthOrganismDetailsImage
REVERSE TRANSCRIPTASE P51 SUBUNIT441Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: pol
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
Expand
  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*TP*TP*TP*TP*TP*CP*TP*TP*TP*TP*GP*TP*TP*AP*TP*TP*GP*TP*GP*GP*CP*C)-3')C [auth D]23Homo sapiens
Sequence Annotations
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  • Reference Sequence

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Entity ID: 4
MoleculeChains LengthOrganismImage
RNA (25-MER)D [auth R]25Homo sapiens
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
EFZ BindingDB:  6BSI Ki: min: 3, max: 3000 (nM) from 20 assay(s)
IC50: min: 0.09, max: 910 (nM) from 48 assay(s)
EC50: min: 1, max: 300 (nM) from 8 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.25 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.195 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 163.85α = 90
b = 163.85β = 90
c = 129.57γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)United States--

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-03
    Type: Initial release
  • Version 1.1: 2018-01-17
    Changes: Author supporting evidence
  • Version 1.2: 2018-04-25
    Changes: Data collection, Database references
  • Version 1.3: 2022-03-23
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.4: 2024-05-22
    Changes: Data collection