4QWB

CRYSTAL STRUCTURE of DPO4 LINKER REGION P236A MUTANT WITH AN INCOMING D-dCDP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.226 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase.

Gaur, V.Vyas, R.Fowler, J.D.Efthimiopoulos, G.Feng, J.Y.Suo, Z.

(2014) Nucleic Acids Res 42: 9984-9995

  • DOI: https://doi.org/10.1093/nar/gku709
  • Primary Citation of Related Structures:  
    4QW8, 4QW9, 4QWA, 4QWB, 4QWC, 4QWD, 4QWE

  • PubMed Abstract: 

    Considering that all natural nucleotides (D-dNTPs) and the building blocks (D-dNMPs) of DNA chains possess D-stereochemistry, DNA polymerases and reverse transcriptases (RTs) likely possess strongD-stereoselectivity by preferably binding and incorporating D-dNTPs over unnatural L-dNTPs during DNA synthesis. Surprisingly, a structural basis for the discrimination against L-dNTPs by DNA polymerases or RTs has not been established although L-deoxycytidine analogs (lamivudine and emtricitabine) and L-thymidine (telbivudine) have been widely used as antiviral drugs for years. Here we report seven high-resolution ternary crystal structures of a prototype Y-family DNA polymerase, DNA, and D-dCTP, D-dCDP, L-dCDP, or the diphosphates and triphosphates of lamivudine and emtricitabine. These structures reveal that relative to D-dCTP, each of these L-nucleotides has its sugar ring rotated by 180° with an unusual O4'-endo sugar puckering and exhibits multiple triphosphate-binding conformations within the active site of the polymerase. Such rare binding modes significantly decrease the incorporation rates and efficiencies of these L-nucleotides catalyzed by the polymerase.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA polymerase IV343Saccharolobus solfataricus P2Mutation(s): 1 
Gene Names: dbhdpo4SSO2448
EC: 2.7.7.7
UniProt
Find proteins for Q97W02 (Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2))
Explore Q97W02 
Go to UniProtKB:  Q97W02
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ97W02
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*GP*CP*TP*AP*CP*AP*GP*GP*AP*CP*TP*(DOC))-3')13N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*TP*TP*CP*AP*GP*GP*AP*GP*TP*CP*CP*TP*GP*TP*AP*GP*CP*C)-3')18N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
YYY
Query on YYY

Download Ideal Coordinates CCD File 
D [auth A]DEOXYCYTIDINE DIPHOSPHATE
C9 H15 N3 O10 P2
FTDHDKPUHBLBTL-SHYZEUOFSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
L [auth A],
M [auth A],
O [auth C]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A],
J [auth A],
K [auth A]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
CA
Query on CA

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A],
N [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.226 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 96.95α = 90
b = 102.34β = 90
c = 52.73γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-08-27
    Type: Initial release
  • Version 1.1: 2014-09-17
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations