2MMS

AG(7-deaza)G FAPY modified duplex

Summary for 2MMS

• Entry DOI: 10.2210/pdb2mms/pdb
• NMR Information: BMRB: 19863
• Descriptor: DNA_(5'-D(*CP*TP*AP*AP*(FAG)P*(7GU)P*TP*TP*CP*A)-3'), DNA_(5'-D(*TP*GP*AP*AP*CP*CP*TP*TP*AP*G)-3') (2 entities in total)
• Functional Keywords: aflatoxin b1, fapy, formamidopyrimidine, intercalation, dna adduct, deoxyribonucleic acid, hydrogen bond, sequence dependence, ag(7-deaza)g, dna
• Total number of polymer chains: 2
• Total formula weight: 6433.33

Authors

Li, L.,Stone, M. (deposition date: 2014-03-17, release date: 2015-02-25, Last modification date: 2024-05-01)

Primary citation

Li, L.,Brown, K.L.,Ma, R.,Stone, M.P.
DNA Sequence Modulates Geometrical Isomerism of the trans-8,9-Dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxy Aflatoxin B1 Adduct.
Chem.Res.Toxicol., 28:225-237, 2015

PubMed Abstract: Aflatoxin B(1) (AFB(1)), a mycotoxin produced by Aspergillus flavus, is oxidized by cytochrome P450 enzymes to aflatoxin B(1)-8,9-epoxide, which alkylates DNA at N7-dG. Under basic conditions, this N7-dG adduct rearranges to yield the trans-8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxy aflatoxin B(1) (AFB(1)−FAPY) adduct. The AFB(1)−FAPY adduct exhibits geometrical isomerism involving the formamide moiety. NMR analyses of duplex oligodeoxynucleotides containing the 5′-XA-3′, 5′-XC-3′, 5′-XT-3′, and 5′-XY-3′ sequences (X = AFB(1)−FAPY; Y = 7-deaza-dG)demonstrate that the equilibrium between E and Z isomers is controlled by major groove hydrogen bonding interactions.Structural analysis of the adduct in the 5′-XA-3′ sequence indicates the preference of the E isomer of the formamide group,attributed to formation of a hydrogen bond between the formyl oxygen and the N(6) exocyclic amino group of the 3′-neighboradenine. While the 5′-XA-3′ sequence exhibits the E isomer, the 5′-XC-3′ sequence exhibits a 7:3 E:Z ratio at equilibrium at 283K. The E isomer is favored by a hydrogen bond between the formyl oxygen and the N(4)-dC exocyclic amino group of the 3′-neighbor cytosine. The 5′-XT-3′ and 5′-XY-3′ sequences cannot form such a hydrogen bond between the formyl oxygen and the 3′-neighbor T or Y, respectively, and in these sequence contexts the Z isomer is favored. Additional equilibria between α and β anomers and the potential to exhibit atropisomers about the C5−N(5) bond do not depend upon sequence. In each of the four DNA sequences, the AFB(1)−FAPY adduct maintains the β deoxyribose configuration. Each of these four sequences feature the atropisomer of the AFB(1) moiety that is intercalated above the 5′-face of the damaged guanine. This enforces the Ra axialc onformation for the C5−N(5) bond.

PubMed: 25587868
DOI: 10.1021/tx5003832

Experimental method

SOLUTION NMR