受损和未受损 DNA 的碱基翻转自由能曲线。
Base flipping free energy profiles for damaged and undamaged DNA.
机构信息
Department of Biology, New York University, New York, New York 10003, USA.
出版信息
Chem Res Toxicol. 2010 Dec 20;23(12):1868-70. doi: 10.1021/tx1003613.
Abstract
Lesion-induced thermodynamic destabilization is believed to facilitate β-hairpin intrusion by the human XPC/hHR23B nucleotide excision repair (NER) recognition factor, accompanied by partner-base flipping, as suggested by the crystal structure of the yeast orthologue (Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575). To investigate this proposed mechanism, we employed the umbrella sampling method to compute partner base flipping free energies for the repair susceptible 14R (+)-trans-anti-DB[a,l]P-N(2)-dG modified duplex 11-mer, derived from the fjord region polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene, and for the undamaged duplex. Our flipping free energy profiles show that the adduct has a lower flipping barrier by ∼7.7 kcal/mol, consistent with its thermally destabilizing impact on the damaged DNA duplex and its susceptibility to NER.
摘要
据信，损伤诱导的热力学不稳定性有助于人类 XPC/hHR23B 核苷酸切除修复（NER）识别因子的β发夹侵入，同时伴有碱基对翻转，这是酵母同源物晶体结构所提示的（Min，J.H.和 Pavletich，N.P.（2007）自然 449，570-575）。为了研究这一拟议的机制，我们采用伞状采样方法计算了修复敏感的 14R（+）-反式-抗-DB[a，l]P-N（2）-dG 修饰的双链 11 -mer 的碱基对翻转自由能，该 11-mer 来自多环芳烃二苯并[a，l]芘的峡湾区域，以及未受损的双链。我们的翻转自由能曲线表明，加合物的翻转势垒降低了约 7.7 kcal/mol，这与它对损伤 DNA 双链的热不稳定性及其对 NER 的易感性一致。
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本文引用的文献
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J Chem Theory Comput. 2006 Jan;2(1):187-200. doi: 10.1021/ct0501957.
2
An Improved Reaction Coordinate for Nucleic Acid Base Flipping Studies.一种用于核酸碱基翻转研究的改进反应坐标。
J Chem Theory Comput. 2009 Nov 10;5(11):3105-13. doi: 10.1021/ct9001575. Epub 2009 Oct 9.
3
Exploring damage recognition models in prokaryotic nucleotide excision repair with a benzo[a]pyrene-derived lesion in UvrB.利用UvrB中苯并[a]芘衍生的损伤探索原核生物核苷酸切除修复中的损伤识别模型。
Biochemistry. 2009 Sep 29;48(38):8948-57. doi: 10.1021/bi9010072.
4
On the impact of the molecule structure in chemical carcinogenesis.论分子结构在化学致癌作用中的影响。
EXS. 2009;99:151-79. doi: 10.1007/978-3-7643-8336-7_6.
5
Recognition of DNA damage by the Rad4 nucleotide excision repair protein.Rad4核苷酸切除修复蛋白对DNA损伤的识别。
Nature. 2007 Oct 4;449(7162):570-5. doi: 10.1038/nature06155. Epub 2007 Sep 19.
6
Refinement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers.用于核酸的AMBER力场的优化：改进α/γ构象异构体的描述。
Biophys J. 2007 Jun 1;92(11):3817-29. doi: 10.1529/biophysj.106.097782. Epub 2007 Mar 9.
7
Structural basis for DNA recognition and processing by UvrB.UvrB对DNA识别与加工的结构基础
Nat Struct Mol Biol. 2006 Apr;13(4):360-4. doi: 10.1038/nsmb1072. Epub 2006 Mar 12.
8
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Chem Rev. 2006 Feb;106(2):489-505. doi: 10.1021/cr040475z.
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Chem Rev. 2006 Feb;106(2):253-76. doi: 10.1021/cr040483f.
10
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