2LWM

Solution Structure of Duplex DNA Containing a b-Carba-Fapy-dG Lesion

Summary for 2LWM

• Entry DOI: 10.2210/pdb2lwm/pdb
• Related: 2LWN 2LWO
• NMR Information: BMRB: 18638
• Descriptor: DNA (5'-D(*CP*GP*TP*AP*C*(LWM)P*CP*AP*TP*GP*C)-3'), DNA (5'-D(*GP*CP*AP*TP*GP*CP*GP*TP*AP*CP*G)-3') (2 entities in total)
• Functional Keywords: oxidative damage, dna
• Total number of polymer chains: 2
• Total formula weight: 6724.44

Authors

Zalianyak, T.,de los Santos, C.,Lukin, M.,Attaluri, S.,Johnson, F. (deposition date: 2012-08-03, release date: 2013-02-20, Last modification date: 2024-05-01)

Primary citation

Lukin, M.,Zaliznyak, T.,Attaluri, S.,Johnson, F.,de Los Santos, C.
Solution Structure of Duplex DNA Containing a b-Carba-Fapy-dG Lesion
Chem.Res.Toxicol., 25:2423-2431, 2012

PubMed Abstract: The addition of hydroxyl radicals to the C8 position of guanine can lead to the formation of a 2,6-diamino-4-hydroxy-5-formamido-2'-deoxypyrimidine (Fapy-dG) lesion, whose endogenous levels in cellular DNA rival those of 8-oxo-7,8-dihydroxy-2'-deoxyguanosine. Despite its prevalence, the structure of duplex DNA containing Fapy-dG is unknown. We have prepared an undecameric duplex containing a centrally located β-cFapy-dG residue paired to dC and determined its solution structure by high-resolution NMR spectroscopy and restrained molecular dynamic simulations. The damaged duplex adopts a right-handed helical structure with all residues in an anti conformation, forming Watson-Crick base pair alignments, and 2-deoxyribose conformations in the C2'-endo/C1'-exo range. The formamido group of Fapy rotates out of the pyrimidine plane and is present in the Z and E configurations that equilibrate with an approximate 2:1 population ratio. The two isomeric duplexes show similar lesion-induced deviations from a canonical B-from DNA conformation that are minor and limited to the central three-base-pair segment of the duplex, affecting the stacking interactions with the 5-lesion-neighboring residue. We discuss the implications of our observations for translesion synthesis during DNA replication and the recognition of Fapy-dG by DNA glycosylases.

PubMed: 22897814
DOI: 10.1021/tx300290b

Experimental method

SOLUTION NMR