2LZK

NMR solution structure of an N2-guanine DNA adduct derived from the potent tumorigen dibenzo[a,l]pyrene: Intercalation from the minor groove with ruptured Watson-Crick base pairing


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 
  • Selection Criteria: structures with the least restraint violations 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Nuclear Magnetic Resonance Solution Structure of an N(2)-Guanine DNA Adduct Derived from the Potent Tumorigen Dibenzo[a,l]pyrene: Intercalation from the Minor Groove with Ruptured Watson-Crick Base Pairing.

Tang, Y.Liu, Z.Ding, S.Lin, C.H.Cai, Y.Rodriguez, F.A.Sayer, J.M.Jerina, D.M.Amin, S.Broyde, S.Geacintov, N.E.

(2012) Biochemistry 51: 9751-9762

  • DOI: https://doi.org/10.1021/bi3013577
  • Primary Citation of Related Structures:  
    2LZK

  • PubMed Abstract: 

    The most potent tumorigen identified among the polycyclic aromatic hydrocarbons (PAH) is the nonplanar fjord region dibenzo[a,l]pyrene (DB[a,l]P). It is metabolically activated in vivo through the widely studied diol epoxide (DE) pathway to form covalent adducts with DNA bases, predominantly guanine and adenine. The (+)-11S,12R,13R,14S DE enantiomer forms adducts via its C14 position with the exocyclic amino group of guanine. Here, we present the first nuclear magnetic resonance solution structure of a DB[a,l]P-derived adduct, the 14R-(+)-trans-anti-DB[a,l]P-N(2)-dG (DB[a,l]P-dG) lesion in double-stranded DNA. In contrast to the stereochemically identical benzo[a]pyrene-derived N(2)-dG adduct (B[a]P-dG) in which the B[a]P rings reside in the B-DNA minor groove on the 3'-side of the modifed deoxyguanosine, in the DB[a,l]P-derived adduct the DB[a,l]P rings intercalate into the duplex on the 3'-side of the modified base from the sterically crowded minor groove. Watson-Crick base pairing of the modified guanine with the partner cytosine is broken, but these bases retain some stacking with the bulky DB[a,l]P ring system. This new theme in PAH DE-DNA adduct conformation differs from (1) the classical intercalation motif in which Watson-Crick base pairing is intact at the lesion site and (2) the base-displaced intercalation motif in which the damaged base and its partner are extruded from the helix. The structural considerations that lead to the intercalated conformation of the DB[a,l]P-dG lesion in contrast to the minor groove alignment of the B[a]P-dG adduct, and the implications of the DB[a,l]P-dG conformational motif for the recognition of such DNA lesions by the human nucleotide excision repair apparatus, are discussed.


  • Organizational Affiliation

    Department of Chemistry, New York University, New York, NY 10003, USA.


Macromolecules

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Entity ID: 1
MoleculeChains LengthOrganismImage
DNA (5'-D(*CP*CP*AP*TP*CP*GP*CP*TP*AP*CP*C)-3')11N/A
Sequence Annotations
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  • Reference Sequence

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*GP*TP*AP*GP*CP*GP*AP*TP*GP*G)-3')11N/A
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
14L
Query on 14L

Download Ideal Coordinates CCD File 
C [auth A](11S,12S,13S)-11,12,13,14-tetrahydronaphtho[1,2,3,4-pqr]tetraphene-11,12,13-triol
C24 H18 O3
HWQNIRBJKZENJU-IGKWTDBASA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 
  • Selection Criteria: structures with the least restraint violations 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-11-21
    Type: Initial release
  • Version 1.1: 2012-11-28
    Changes: Database references
  • Version 1.2: 2013-02-20
    Changes: Database references
  • Version 1.3: 2023-06-14
    Changes: Data collection, Database references, Derived calculations, Other