1XC9

Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.221 

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Literature

Structure of a High Fidelity DNA Polymerase Bound to a Benzo[a]pyrene Adduct That Blocks Replication

Hsu, G.W.Huang, X.Luneva, N.P.Geacintov, N.E.Beese, L.S.

(2005) J Biol Chem 280: 3764-3770

  • DOI: https://doi.org/10.1074/jbc.M411276200
  • Primary Citation of Related Structures:  
    1XC9

  • PubMed Abstract: 

    Of the carcinogens to which humans are most frequently exposed, the polycyclic aromatic hydrocarbon benzo[a]pyrene (BP) is one of the most ubiquitous. BP is a byproduct of grilled foods and tobacco and fuel combustion and has long been linked to various human cancers, particularly lung and skin. BP is metabolized to diol epoxides that covalently modify DNA bases to form bulky adducts that block DNA synthesis by replicative or high fidelity DNA polymerases. Here we present the structure of a high fidelity polymerase from a thermostable strain of Bacillus stearothermophilus (Bacillus fragment) bound to the most common BP-derived N2-guanine adduct base-paired with cytosine. The BP adduct adopts a conformation that places the polycyclic BP moiety in the nascent DNA minor groove and is the first structure of a minor groove adduct bound to a polymerase. Orientation of the BP moiety into the nascent DNA minor groove results in extensive disruption to the interactions between the adducted DNA duplex and the polymerase. The disruptions revealed by the structure of Bacillus fragment bound to a BP adduct provide a molecular basis for rationalizing the potent blocking effect on replication exerted by BP adducts.


  • Organizational Affiliation

    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.


Macromolecules

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
DNA polymerase IC [auth A]580Geobacillus stearothermophilusMutation(s): 0 
EC: 2.7.7.7
UniProt
Find proteins for P52026 (Geobacillus stearothermophilus)
Explore P52026 
Go to UniProtKB:  P52026
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP52026
Sequence Annotations
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  • Reference Sequence

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Entity ID: 1
MoleculeChains LengthOrganismImage
DNA primer strandA [auth B]10N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA template strand with benzo[a]pyrene adductB [auth C]15N/A
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose
D
2N/A
Glycosylation Resources
GlyTouCan:  G05551OP
GlyCosmos:  G05551OP
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.221 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.752α = 90
b = 93.733β = 90
c = 104.512γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-12-14
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2023-08-23
    Changes: Data collection, Database references, Refinement description, Structure summary