4QWC

Ternary Crystal Structures of a Y-family DNA polymerase DPO4 from Sulfobus Solfataricus in Comples with DNA and L-DCDP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.230 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 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

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA polymerase IV
A, D
343Saccharolobus solfataricus P2Mutation(s): 0 
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
Expand
  • Reference Sequence

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*GP*CP*TP*AP*CP*AP*GP*GP*AP*CP*TP*C)-3')
B, E
13synthetic construct
Sequence Annotations
Expand
  • Reference Sequence

Find similar nucleic acids by:  Sequence   |   3D Structure  

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')
C, F
18synthetic construct
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LTP
Query on LTP

Download Ideal Coordinates CCD File 
K [auth A],
P [auth D]
4-amino-1-{2-deoxy-5-O-[(R)-hydroxy(phosphonooxy)phosphoryl]-beta-L-erythro-pentofuranosyl}pyrimidin-2(1H)-one
C9 H15 N3 O10 P2
FTDHDKPUHBLBTL-CHKWXVPMSA-N
ACT
Query on ACT

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

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
L [auth D],
M [auth D],
N [auth D]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.230 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.44α = 90
b = 101.93β = 90
c = 105.4γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



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 2.0: 2022-04-20
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Refinement description, Source and taxonomy, Structure summary
  • Version 2.1: 2023-09-20
    Changes: Data collection, Refinement description