2KH5

Solution Structure of cis-5R,6S-thymine glycol opposite complementary adenine in duplex DNA

Summary for 2KH5

• Entry DOI: 10.2210/pdb2kh5/pdb
• Related: 2KH6
• Descriptor: 5'-D(*GP*TP*GP*CP*GP*(CTG)P*GP*TP*TP*TP*GP*T)-3', 5'-D(*AP*CP*AP*AP*AP*CP*AP*CP*GP*CP*AP*C)-3' (2 entities in total)
• Functional Keywords: thymine glycol, dna
• Total number of polymer chains: 2
• Total formula weight: 7358.82

Authors

Brown, K.L. (deposition date: 2009-03-24, release date: 2010-03-02, Last modification date: 2024-05-22)

Primary citation

Brown, K.L.,Roginskaya, M.,Zou, Y.,Altamirano, A.,Basu, A.K.,Stone, M.P.
Binding of the human nucleotide excision repair proteins XPA and XPC/HR23B to the 5R-thymine glycol lesion and structure of the cis-(5R,6S) thymine glycol epimer in the 5'-GTgG-3' sequence: destabilization of two base pairs at the lesion site
Nucleic Acids Res., 38:428-440, 2010

PubMed Abstract: The 5R thymine glycol (5R-Tg) DNA lesion exists as a mixture of cis-(5R,6S) and trans-(5R,6R) epimers; these modulate base excision repair. We examine the 7:3 cis-(5R,6S):trans-(5R,6R) mixture of epimers paired opposite adenine in the 5'-GTgG-3' sequence with regard to nucleotide excision repair. Human XPA recognizes the lesion comparably to the C8-dG acetylaminoflourene (AAF) adduct, whereas XPC/HR23B recognition of Tg is superior. 5R-Tg is processed by the Escherichia coli UvrA and UvrABC proteins less efficiently than the C8-dG AAF adduct. For the cis-(5R, 6S) epimer Tg and A are inserted into the helix, remaining in the Watson-Crick alignment. The Tg N3H imine and A N(6) amine protons undergo increased solvent exchange. Stacking between Tg and the 3'-neighbor G*C base pair is disrupted. The solvent accessible surface and T(2) relaxation of Tg increases. Molecular dynamics calculations predict that the axial conformation of the Tg CH(3) group is favored; propeller twisting of the Tg*A pair and hydrogen bonding between Tg OH6 and the N7 atom of the 3'-neighbor guanine alleviate steric clash with the 5'-neighbor base pair. Tg also destabilizes the 5'-neighbor G*C base pair. This may facilitate flipping both base pairs from the helix, enabling XPC/HR23B recognition prior to recruitment of XPA.

PubMed: 19892827
DOI: 10.1093/nar/gkp844

Experimental method

SOLUTION NMR