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

Summary for 2LZK

• Entry DOI: 10.2210/pdb2lzk/pdb
• NMR Information: BMRB: 18762
• Descriptor: DNA (5'-D(*CP*CP*AP*TP*CP*GP*CP*TP*AP*CP*C)-3'), DNA (5'-D(*GP*GP*TP*AP*GP*CP*GP*AP*TP*GP*G)-3'), (11S,12S,13S)-11,12,13,14-tetrahydronaphtho[1,2,3,4-pqr]tetraphene-11,12,13-triol (3 entities in total)
• Functional Keywords: 14r (+)-trans-anti-db[a, l]p-n2-dg, dna adduct, dna
• Total number of polymer chains: 2
• Total formula weight: 7062.79

Authors

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. (deposition date: 2012-10-04, release date: 2012-11-21, Last modification date: 2024-05-15)

Primary citation

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.
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, 2012

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.

PubMed: 23121427
DOI: 10.1021/bi3013577

Experimental method

SOLUTION NMR