• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

γ-羟基丙基脱氧鸟苷与EcoRI之间DNA-蛋白质交联的形成

Formation of DNA-protein cross-links between gamma-hydroxypropanodeoxyguanosine and EcoRI.

作者信息

VanderVeen Laurie A, Harris Thomas M, Jen-Jacobson Linda, Marnett Lawrence J

机构信息

A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

出版信息

Chem Res Toxicol. 2008 Sep;21(9):1733-8. doi: 10.1021/tx800092g. Epub 2008 Aug 9.

DOI:10.1021/tx800092g
PMID:18690724
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2651693/
Abstract

The toxicity of acrolein, an alpha,beta-unsaturated aldehyde produced during lipid peroxidation, is attributable to its high reactivity toward DNA and cellular proteins. The major acrolein-DNA adduct, gamma-hydroxypropano-2'-deoxyguanosine (gamma-HOPdG), ring opens to form a reactive N(2)-oxopropyl moiety that cross-links to DNA and proteins. We demonstrate the ability of gamma-HOPdG in a duplex oligonucleotide to cross-link to a protein (EcoRI) that specifically interacts with DNA at a unique sequence. The formation of a cross-link to EcoRI was dependent on the intimate binding of the enzyme to its gamma-HOPdG-modified recognition site. Interestingly, the cross-link did not restrict the ability of EcoRI to cleave DNA substrates. However, stabilization of the cross-link by reduction of the Schiff base linkage resulted in loss of enzyme activity. This work indicates that the gamma-HOPdG-EcoRI cross-link is in equilibrium with free oligonucleotide and enzyme. Reversal of cross-link formation allows EcoRI to effect enzymatic cleavage of competitor oligonucleotides.

摘要

丙烯醛是脂质过氧化过程中产生的一种α,β-不饱和醛，其毒性归因于它对DNA和细胞蛋白质的高反应活性。主要的丙烯醛-DNA加合物γ-羟基丙基-2'-脱氧鸟苷（γ-HOPdG）会发生环开环反应，形成一个可与DNA和蛋白质交联的反应性N(2)-氧代丙基部分。我们证明了双链寡核苷酸中的γ-HOPdG能够与一种在特定序列与DNA特异性相互作用的蛋白质（EcoRI）发生交联。与EcoRI的交联形成取决于该酶与其γ-HOPdG修饰的识别位点的紧密结合。有趣的是，这种交联并不限制EcoRI切割DNA底物的能力。然而，通过还原席夫碱连接来稳定交联会导致酶活性丧失。这项工作表明γ-HOPdG-EcoRI交联与游离寡核苷酸和酶处于平衡状态。交联形成的逆转使EcoRI能够对竞争寡核苷酸进行酶切。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/3bdaca9d0ae1/tx-2008-00092g_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/6fbea9d66a39/tx-2008-00092g_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/96c003c84c45/tx-2008-00092g_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/ecb5d1fd989f/tx-2008-00092g_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/cce05da956b1/tx-2008-00092g_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/3bdaca9d0ae1/tx-2008-00092g_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/6fbea9d66a39/tx-2008-00092g_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/96c003c84c45/tx-2008-00092g_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/ecb5d1fd989f/tx-2008-00092g_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/cce05da956b1/tx-2008-00092g_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ffd/2651693/3bdaca9d0ae1/tx-2008-00092g_0005.jpg

相似文献

1
Formation of DNA-protein cross-links between gamma-hydroxypropanodeoxyguanosine and EcoRI.γ-羟基丙基脱氧鸟苷与EcoRI之间DNA-蛋白质交联的形成
Chem Res Toxicol. 2008 Sep;21(9):1733-8. doi: 10.1021/tx800092g. Epub 2008 Aug 9.
2
Comparative evaluation of the bioreactivity and mutagenic spectra of acrolein-derived alpha-HOPdG and gamma-HOPdG regioisomeric deoxyguanosine adducts.丙烯醛衍生的α-HOPdG和γ-HOPdG区域异构脱氧鸟苷加合物的生物反应性和诱变谱的比较评估。
Chem Res Toxicol. 2003 Aug;16(8):1019-28. doi: 10.1021/tx034066u.
3
Differential DNA recognition and cleavage by EcoRI dependent on the dynamic equilibrium between the two forms of the malondialdehyde-deoxyguanosine adduct.EcoRI对DNA的差异性识别与切割取决于丙二醛-脱氧鸟苷加合物两种形式之间的动态平衡。
Biochemistry. 2005 Apr 5;44(13):5024-33. doi: 10.1021/bi0472898.
4
Spectroscopic characterization of interstrand carbinolamine cross-links formed in the 5'-CpG-3' sequence by the acrolein-derived gamma-OH-1,N2-propano-2'-deoxyguanosine DNA adduct.由丙烯醛衍生的γ-羟基-1,N2-丙基-2'-脱氧鸟苷DNA加合物在5'-CpG-3'序列中形成的链间甲醇胺交联的光谱表征。
J Am Chem Soc. 2005 Dec 21;127(50):17686-96. doi: 10.1021/ja053897e.
5
Mutagenicity of acrolein and acrolein-induced DNA adducts.丙烯醛的致突变性及其诱导的 DNA 加合物。
Toxicol Mech Methods. 2010 Jan;20(1):36-44. doi: 10.3109/15376510903530845.
6
Error prone translesion synthesis past gamma-hydroxypropano deoxyguanosine, the primary acrolein-derived adduct in mammalian cells.易错跨损伤合成绕过γ-羟基丙基脱氧鸟苷，这是哺乳动物细胞中主要的丙烯醛衍生加合物。
J Biol Chem. 2002 May 24;277(21):18257-65. doi: 10.1074/jbc.M112419200. Epub 2002 Mar 11.
7
Human DNA polymerase iota promotes replication through a ring-closed minor-groove adduct that adopts a syn conformation in DNA.人类DNA聚合酶ι通过一种在DNA中呈顺式构象的环状封闭小沟加合物促进复制。
Mol Cell Biol. 2005 Oct;25(19):8748-54. doi: 10.1128/MCB.25.19.8748-8754.2005.
8
Stereospecific formation of interstrand carbinolamine DNA cross-links by crotonaldehyde- and acetaldehyde-derived alpha-CH3-gamma-OH-1,N2-propano-2'-deoxyguanosine adducts in the 5'-CpG-3' sequence.巴豆醛和乙醛衍生的α-CH3-γ-OH-1,N2-丙基-2'-脱氧鸟苷加合物在5'-CpG-3'序列中立体特异性形成链间甲醇胺DNA交联。
Chem Res Toxicol. 2006 Feb;19(2):195-208. doi: 10.1021/tx050239z.
9
Translesion synthesis past acrolein-derived DNA adduct, gamma -hydroxypropanodeoxyguanosine, by yeast and human DNA polymerase eta.酵母和人类DNA聚合酶η跨越丙烯醛衍生的DNA加合物γ-羟基丙基脱氧鸟苷进行跨损伤合成。
J Biol Chem. 2003 Jan 10;278(2):784-90. doi: 10.1074/jbc.M207774200. Epub 2002 Oct 24.
10
Stereospecific formation of the (R)-gamma-hydroxytrimethylene interstrand N2-dG:N2-dG cross-link arising from the gamma-OH-1,N2-propano-2'-deoxyguanosine adduct in the 5'-CpG-3' DNA sequence.在5'-CpG-3' DNA序列中，由γ-OH-1,N2-丙基-2'-脱氧鸟苷加合物产生的（R）-γ-羟基三亚甲基链间N2-dG:N2-dG交联的立体特异性形成。
J Am Chem Soc. 2009 Jun 24;131(24):8416-24. doi: 10.1021/ja809543j.

引用本文的文献

1
DNA-Protein Cross-Links: Formation, Structural Identities, and Biological Outcomes.DNA-蛋白质交联：形成、结构特征及生物学结果
Acc Chem Res. 2015 Jun 16;48(6):1631-44. doi: 10.1021/acs.accounts.5b00056. Epub 2015 Jun 2.
2
Synthesis of site-specific DNA-protein conjugates and their effects on DNA replication.位点特异性DNA-蛋白质缀合物的合成及其对DNA复制的影响。
ACS Chem Biol. 2014 Aug 15;9(8):1860-8. doi: 10.1021/cb5001795. Epub 2014 Jun 26.
3
Characterization of the deoxyguanosine-lysine cross-link of methylglyoxal.甲基乙二醛的脱氧鸟苷-赖氨酸交联的表征

本文引用的文献

1
Chemical properties of oxopropenyl adducts of purine and pyrimidine nucleosides and their reactivity toward amino acid cross-link formation.嘌呤和嘧啶核苷的氧丙烯基加合物的化学性质及其对氨基酸交联形成的反应活性。
J Am Chem Soc. 2008 Feb 20;130(7):2195-201. doi: 10.1021/ja074506u. Epub 2008 Jan 29.
2
Oxidative stress and neurotoxicity.氧化应激与神经毒性。
Chem Res Toxicol. 2008 Jan;21(1):172-88. doi: 10.1021/tx700210j. Epub 2007 Dec 4.
3
Mutagenic potential of DNA-peptide crosslinks mediated by acrolein-derived DNA adducts.
Chem Res Toxicol. 2014 Jun 16;27(6):1019-29. doi: 10.1021/tx500068v. Epub 2014 May 15.
4
Formation of fused-ring 2'-deoxycytidine adducts from 1-chloro-3-buten-2-one, an in vitro 1,3-butadiene metabolite, under in vitro physiological conditions.在体外生理条件下，1-氯-3-丁烯-2-酮（一种 1,3-丁二烯的代谢物）形成融合环 2'-脱氧胞苷加合物。
Chem Res Toxicol. 2013 Oct 21;26(10):1545-53. doi: 10.1021/tx4002435. Epub 2013 Sep 25.
5
Synthesis of sequence-specific DNA-protein conjugates via a reductive amination strategy.通过还原胺化策略合成序列特异性 DNA-蛋白质缀合物。
Bioconjug Chem. 2013 Sep 18;24(9):1496-506. doi: 10.1021/bc400018u. Epub 2013 Aug 16.
6
Analysis of acrolein-derived 1,N2-propanodeoxyguanosine adducts in human leukocyte DNA from smokers and nonsmokers.分析吸烟与非吸烟人群白细胞 DNA 中丙烯醛衍生的 1,N2-丙二脱氧鸟苷加合物。
Chem Res Toxicol. 2011 Jan 14;24(1):119-24. doi: 10.1021/tx100321y. Epub 2010 Nov 22.
7
Impact of alpha-hydroxy-propanodeoxyguanine adducts on DNA duplex energetics: opposite base modulation and implications for mutagenicity and genotoxicity.alpha-羟基-丙烷脱氧鸟嘌呤加合物对 DNA 双链体能量学的影响：碱基的相反调节及其对致突变性和遗传毒性的影响。
Biopolymers. 2010 Apr;93(4):370-82. doi: 10.1002/bip.21355.
8
Chemistry and biology of DNA containing 1,N(2)-deoxyguanosine adducts of the alpha,beta-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal.含有α,β-不饱和醛（丙烯醛、巴豆醛和4-羟基壬烯醛）的1,N(2)-脱氧鸟苷加合物的DNA的化学与生物学特性
Chem Res Toxicol. 2009 May;22(5):759-78. doi: 10.1021/tx9000489.
由丙烯醛衍生的DNA加合物介导的DNA-肽交联的诱变潜力。
Mutat Res. 2008 Jan 1;637(1-2):161-72. doi: 10.1016/j.mrfmmm.2007.08.001. Epub 2007 Aug 7.
4
Future of toxicology--lipidomics, an important emerging area for toxicologists: focus on lipid oxidation products.毒理学的未来——脂质组学，毒理学家的一个重要新兴领域：聚焦于脂质氧化产物
Chem Res Toxicol. 2007 Jun;20(6):849-53. doi: 10.1021/tx7000652. Epub 2007 May 10.
5
Detection and quantitation of acrolein-derived 1,N2-propanodeoxyguanosine adducts in human lung by liquid chromatography-electrospray ionization-tandem mass spectrometry.采用液相色谱-电喷雾电离-串联质谱法检测和定量人肺中丙烯醛衍生的1,N2-丙烷脱氧鸟苷加合物
Chem Res Toxicol. 2007 Apr;20(4):565-71. doi: 10.1021/tx700023z. Epub 2007 Mar 27.
6
Structure of T4 pyrimidine dimer glycosylase in a reduced imine covalent complex with abasic site-containing DNA.T4嘧啶二聚体糖基化酶与含无碱基位点DNA形成的还原亚胺共价复合物的结构
J Mol Biol. 2006 Sep 15;362(2):241-58. doi: 10.1016/j.jmb.2006.06.059. Epub 2006 Jul 7.
7
Stereospecific formation of interstrand carbinolamine DNA cross-links by crotonaldehyde- and acetaldehyde-derived alpha-CH3-gamma-OH-1,N2-propano-2'-deoxyguanosine adducts in the 5'-CpG-3' sequence.巴豆醛和乙醛衍生的α-CH3-γ-OH-1,N2-丙基-2'-脱氧鸟苷加合物在5'-CpG-3'序列中立体特异性形成链间甲醇胺DNA交联。
Chem Res Toxicol. 2006 Feb;19(2):195-208. doi: 10.1021/tx050239z.
8
Spectroscopic characterization of interstrand carbinolamine cross-links formed in the 5'-CpG-3' sequence by the acrolein-derived gamma-OH-1,N2-propano-2'-deoxyguanosine DNA adduct.由丙烯醛衍生的γ-羟基-1,N2-丙基-2'-脱氧鸟苷DNA加合物在5'-CpG-3'序列中形成的链间甲醇胺交联的光谱表征。
J Am Chem Soc. 2005 Dec 21;127(50):17686-96. doi: 10.1021/ja053897e.
9
Differential DNA recognition and cleavage by EcoRI dependent on the dynamic equilibrium between the two forms of the malondialdehyde-deoxyguanosine adduct.EcoRI对DNA的差异性识别与切割取决于丙二醛-脱氧鸟苷加合物两种形式之间的动态平衡。
Biochemistry. 2005 Apr 5;44(13):5024-33. doi: 10.1021/bi0472898.
10
Mechanisms of coupling between DNA recognition specificity and catalysis in EcoRI endonuclease.大肠杆菌 EcoRI 核酸内切酶中 DNA 识别特异性与催化作用之间的偶联机制。
Structure. 2004 Oct;12(10):1775-88. doi: 10.1016/j.str.2004.07.016.