High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications.
A high-resolution crystal structure is reported for d(TpA)*, the intramolecular thymine-adenine photoadduct that is produced by direct ultraviolet excitation of the dinucleoside monophosphate d(TpA). It confirms the presence of a central 1,3-diazacyclooctatriene ring linking the remnants of the T and A bases, as previously deduced from heteronuclear NMR measurements by Zhao et al. (The structure of d(TpA)*, the major photoproduct of thymidylyl-(3'-5')-deoxyadenosine. Nucleic Acids Res., 1996, 24, 1554-1560). Within the crystal, the d(TpA)* molecules exist as zwitterions with a protonated amidine fragment of the eight-membered ring neutralizing the charge of the internucleotide phosphate monoanion. The absolute configuration at the original thymine C5 and C6 atoms is determined as 5S,6R. This is consistent with d(TpA)* arising by valence isomerization of a precursor cyclobutane photoproduct with cis-syn stereochemistry that is generated by [2 + 2] photoaddition of the thymine 5,6-double bond across the C6 and C5 positions of adenine. This mode of photoaddition should be favoured by the stacked conformation of adjacent T and A bases in B-form DNA. It is probable that the primary photoreaction is mechanistically analogous to pyrimidine dimerization despite having a much lower quantum yield.
Davies
R Jeremy H
RJ
School of Biological Sciences, School of Chemistry and Chemical Engineering, Queen's University, Belfast BT7 1NN, UK. j.davies@qub.ac.uk
Malone
John F
JF
Gan
Yu
Y
Cardin
Christine J
CJ
Lee
Michael P H
MP
Neidle
Stephen
S
D018360:Crystallography, X-Ray; D018736:DNA Adducts / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry*; D008958:Models, Molecular; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013237:Stereoisomerism
D018736:DNA Adducts; D006576:Heterocyclic Compounds, 4 or More Rings; D009838:Oligodeoxyribonucleotides; C519159:d(TpA) thymine-adenine photoadduct