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PDBsum entry 2lzk

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dna_rna ligands links
DNA PDB id
2lzk
Jmol
Contents
DNA/RNA
Ligands
14L
PDB id:
2lzk
Name: DNA
Title: Nmr solution structure of an n2-guanine DNA adduct derived f potent tumorigen dibenzo[a,l]pyrene: intercalation from the groove with ruptured watson-crick base pairing
Structure: DNA (5'-d( Cp Cp Ap Tp Cp Gp Cp Tp Ap Cp C)-3'). Chain: a. Engineered: yes. DNA (5'-d( Gp Gp Tp Ap Gp Cp Gp Ap Tp Gp G)-3'). Chain: b. Engineered: yes
Source: Synthetic: yes. Synthetic: yes
NMR struc: 5 models
Authors: Y.Tang,Z.Liu,S.Ding,C.H.Lin,Y.Cai,F.A.Rodriguez,J.M.Sayer,D. S.Amin,S.Broyde,N.E.Geacintov
Key ref: Y.Tang et al. (2012). 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. Biochemistry, 51, 9751-9762. PubMed id: 23121427
Date:
04-Oct-12     Release date:   21-Nov-12    
 Headers
 References

 

 
Biochemistry 51:9751-9762 (2012)
PubMed id: 23121427  
 
 
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.
Y.Tang, Z.Liu, S.Ding, C.H.Lin, Y.Cai, F.A.Rodriguez, J.M.Sayer, D.M.Jerina, S.Amin, S.Broyde, N.E.Geacintov.
 
  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.