title: Structural and energetic consequences of oxidation of d(ApGpGpGpTpT) telomere repeat unit in complex with TRF1 protein.
abstract: The configuration hyperspace of canonical and oxidized 14-mers of B-DNA comprising telomere repeat units d(ApGpGpGpTpT) was sampled over 40 ns via molecular dynamic (MD) simulations. The energetic and structural consequences of TRF1 binding to telomere B-DNA were compared with non-complexed systems. Energetic properties of analyzed pairs, di- and tri-nucleotide steps occurring in central telomere repeat unit were estimated by means of advanced quantum chemistry computations including not only BSSE corrections, electron correlation contributions but also non-negligible many-body terms. These data along with bases pair and base step parameters distributions allow for quantization of consequences of oxidation and/or TRF1 binding to telomere repeat units. Occurrence of 8-oxoguanine in central telomeric triad (CTT) is the source of high stiffness if compared to non-modified oligomer. The origin of this property comes from significantly alteration of intermolecular interactions introduced by 8-oxoguanine. The increased stability observed for base-base interactions are accumulated and characterizes also di- and tri-nucleotides. The observed changes in the intermolecular interactions originate from structural alterations imposed by TRF1 binding to canonical and oxidized telomere B-DNA. First and most direct consequence of TRF1 binding to oxidized telomere repeat unit is alteration of shift-slide correlations if compared to canonical system. This in turn leads to large differences in purine-purine overlapping in oxidized structures. Thus, oxidized telomere B-DNA double strands are sensitive to interactions with protein ligands and numerous structural and energetic changes are imposed on base pairs forming CTT.
authors.affiliation: Physical Chemistry Department, Collegium Medicum, Nicolaus Copernicus University, Kurpińskiego 5, 85-950, Bydgoszcz, Poland. piotr.cysewski@cm.umk.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Cysewski
authors.forename: Przemysław
authors.initials: P
authors.lastname: Czeleń
mesh_terms: D001483:Base Sequence; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011485:Protein Binding; D011687:Purines / Q000378:metabolism; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D011687:Purines; D035321:Telomeric Repeat Binding Protein 1
references.citation: J Am Chem Soc. 2005 Oct 12;127(40):13906-18
references.pmid: 16201812
references.citation: Nat Genet. 1997 Oct;17(2):231-5
references.pmid: 9326950
references.citation: Mol Cell. 2001 Aug;8(2):351-61
references.pmid: 11545737
references.citation: Science. 1995 Dec 8;270(5242):1663-7
references.pmid: 7502076
references.citation: Chem Rev. 1999 Nov 10;99(11):3247-76
references.pmid: 11749516
references.citation: J Am Chem Soc. 2002 Oct 2;124(39):11802-8
references.pmid: 12296748
references.citation: J Mol Biol. 1989 Feb 20;205(4):787-91
references.pmid: 2926825
references.citation: Phys Chem Chem Phys. 2005 Apr 21;7(8):1624-6
references.pmid: 19787917
references.citation: J Biomol Struct Dyn. 2002 Apr;19(5):839-51
references.pmid: 11922839
references.citation: Acc Chem Res. 2000 Dec;33(12):889-97
references.pmid: 11123888
references.citation: EMBO Rep. 2005 Jan;6(1):39-45
references.pmid: 15608617
references.citation: J Mol Model. 2007 Jul;13(6-7):739-50
references.pmid: 17340111
references.citation: J Comput Chem. 2005 Dec;26(16):1668-88
references.pmid: 16200636
references.citation: J Mol Model. 2009 Jun;15(6):607-13
references.pmid: 19132417
references.citation: Annu Rev Phys Chem. 2000;51:435-71
references.pmid: 11031289
references.citation: Nature. 2000 Feb 24;403(6772):859-66
references.pmid: 10706276
references.citation: Biophys J. 1992 Sep;63(3):751-9
references.pmid: 1384741
references.citation: Hum Mol Genet. 2003 Feb 1;12(3):227-32
references.pmid: 12554677
references.citation: Structure. 2001 Dec;9(12):1237-51
references.pmid: 11738049
references.citation: Protein Sci. 2005 Jan;14(1):119-30
references.pmid: 15608118
references.citation: J Comput Chem. 2005 Jun;26(8):788-98
references.pmid: 15806602
references.citation: Curr Opin Struct Biol. 2002 Apr;12(2):190-6
references.pmid: 11959496
references.citation: Biophys J. 2006 Jul 1;91(1):164-72
references.pmid: 16617086
references.citation: Nucleic Acids Res. 2003 Sep 1;31(17):5108-21
references.pmid: 12930962
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14771-5
references.pmid: 15465909
references.citation: Science. 1998 Jan 16;279(5349):349-52
references.pmid: 9454332
references.citation: Biophys J. 2007 Jun 1;92(11):3817-29
references.pmid: 17351000
references.citation: Phys Rev Lett. 1995 Jul 3;75(1):168-171
references.pmid: 10059142
references.citation: J Am Chem Soc. 2003 May 21;125(20):6331-6
references.pmid: 12785867
references.citation: J Chem Inf Comput Sci. 2003 May-Jun;43(3):810-8
references.pmid: 12767138
references.citation: Trends Biochem Sci. 2002 Jul;27(7):339-44
references.pmid: 12114022
references.citation: J Chem Theory Comput. 2007 Nov;3(6):2312-34
references.pmid: 26636222
references.citation: J Comput Chem. 2003 May;24(7):898-907
references.pmid: 12692799
references.citation: Nucleic Acids Res. 2005 Feb 24;33(4):1230-9
references.pmid: 15731343
references.citation: J Phys Chem B. 2010 Apr 15;114(14):4789-801
references.pmid: 20307074
references.citation: Nat Struct Biol. 2002 Sep;9(9):646-52
references.pmid: 12198485
references.citation: Lab Invest. 2000 Nov;80(11):1739-47
references.pmid: 11092534
references.citation: Comput Biol Chem. 2003 Jul;27(3):431-41
references.pmid: 12927117
references.citation: J Mol Model. 2009 Jun;15(6):597-606
references.pmid: 19039609
references.citation: Mutat Res. 2000 Jun 30;451(1-2):227-40
references.pmid: 10915875
references.citation: Mutat Res. 2001 Dec 19;487(3-4):93-108
references.pmid: 11738936
references.citation: Nature. 1990 May 31;345(6274):458-60
references.pmid: 2342578