Cargando…

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 an...

Descripción completa

Detalles Bibliográficos
Autores principales: Davies, R. Jeremy H., Malone, John F., Gan, Yu, Cardin, Christine J., Lee, Michael P.H., Neidle, Stephen
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851629/
https://www.ncbi.nlm.nih.gov/pubmed/17264133
http://dx.doi.org/10.1093/nar/gkl1101
_version_ 1782132970522411008
author Davies, R. Jeremy H.
Malone, John F.
Gan, Yu
Cardin, Christine J.
Lee, Michael P.H.
Neidle, Stephen
author_facet Davies, R. Jeremy H.
Malone, John F.
Gan, Yu
Cardin, Christine J.
Lee, Michael P.H.
Neidle, Stephen
author_sort Davies, R. Jeremy H.
collection PubMed
description 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.
format Text
id pubmed-1851629
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-18516292007-04-26 High-resolution crystal structure of the intramolecular d(TpA) thymine–adenine photoadduct and its mechanistic implications Davies, R. Jeremy H. Malone, John F. Gan, Yu Cardin, Christine J. Lee, Michael P.H. Neidle, Stephen Nucleic Acids Res Structural Biology 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. Oxford University Press 2007-02 2007-01-30 /pmc/articles/PMC1851629/ /pubmed/17264133 http://dx.doi.org/10.1093/nar/gkl1101 Text en © 2007 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Davies, R. Jeremy H.
Malone, John F.
Gan, Yu
Cardin, Christine J.
Lee, Michael P.H.
Neidle, Stephen
High-resolution crystal structure of the intramolecular d(TpA) thymine–adenine photoadduct and its mechanistic implications
title High-resolution crystal structure of the intramolecular d(TpA) thymine–adenine photoadduct and its mechanistic implications
title_full High-resolution crystal structure of the intramolecular d(TpA) thymine–adenine photoadduct and its mechanistic implications
title_fullStr High-resolution crystal structure of the intramolecular d(TpA) thymine–adenine photoadduct and its mechanistic implications
title_full_unstemmed High-resolution crystal structure of the intramolecular d(TpA) thymine–adenine photoadduct and its mechanistic implications
title_short High-resolution crystal structure of the intramolecular d(TpA) thymine–adenine photoadduct and its mechanistic implications
title_sort high-resolution crystal structure of the intramolecular d(tpa) thymine–adenine photoadduct and its mechanistic implications
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851629/
https://www.ncbi.nlm.nih.gov/pubmed/17264133
http://dx.doi.org/10.1093/nar/gkl1101
work_keys_str_mv AT daviesrjeremyh highresolutioncrystalstructureoftheintramoleculardtpathymineadeninephotoadductanditsmechanisticimplications
AT malonejohnf highresolutioncrystalstructureoftheintramoleculardtpathymineadeninephotoadductanditsmechanisticimplications
AT ganyu highresolutioncrystalstructureoftheintramoleculardtpathymineadeninephotoadductanditsmechanisticimplications
AT cardinchristinej highresolutioncrystalstructureoftheintramoleculardtpathymineadeninephotoadductanditsmechanisticimplications
AT leemichaelph highresolutioncrystalstructureoftheintramoleculardtpathymineadeninephotoadductanditsmechanisticimplications
AT neidlestephen highresolutioncrystalstructureoftheintramoleculardtpathymineadeninephotoadductanditsmechanisticimplications