从DNA中酶促切除N1-甲基腺嘌呤和N3-甲基胞嘧啶的结构基础。
Structural basis for enzymatic excision of N1-methyladenine and N3-methylcytosine from DNA.
作者信息
Leiros Ingar, Nabong Marivi P, Grøsvik Kristin, Ringvoll Jeanette, Haugland Gyri T, Uldal Lene, Reite Karen, Olsbu Inger K, Knaevelsrud Ingeborg, Moe Elin, Andersen Ole A, Birkeland Nils-Kåre, Ruoff Peter, Klungland Arne, Bjelland Svein
机构信息
The Norwegian Structural Biology Centre, University of Tromsø, Tromsø, Norway.
出版信息
EMBO J. 2007 Apr 18;26(8):2206-17. doi: 10.1038/sj.emboj.7601662. Epub 2007 Mar 29.
Abstract
N(1)-methyladenine (m(1)A) and N(3)-methylcytosine (m(3)C) are major toxic and mutagenic lesions induced by alkylation in single-stranded DNA. In bacteria and mammals, m(1)A and m(3)C were recently shown to be repaired by AlkB-mediated oxidative demethylation, a direct DNA damage reversal mechanism. No AlkB gene homologues have been identified in Archaea. We report that m(1)A and m(3)C are repaired by the AfAlkA base excision repair glycosylase of Archaeoglobus fulgidus, suggesting a different repair mechanism for these lesions in the third domain of life. In addition, AfAlkA was found to effect a robust excision of 1,N(6)-ethenoadenine. We present a high-resolution crystal structure of AfAlkA, which, together with the characterization of several site-directed mutants, forms a molecular rationalization for the newly discovered base excision activity.
摘要
N(1)-甲基腺嘌呤（m(1)A）和N(3)-甲基胞嘧啶（m(3)C）是单链DNA烷基化诱导产生的主要毒性和致突变损伤。在细菌和哺乳动物中，最近发现m(1)A和m(3)C可通过AlkB介导的氧化去甲基化进行修复，这是一种直接的DNA损伤逆转机制。在古菌中尚未鉴定出AlkB基因同源物。我们报告说，嗜热栖热放线菌的AfAlkA碱基切除修复糖基化酶可修复m(1)A和m(3)C，这表明在生命的第三个域中这些损伤存在不同的修复机制。此外，发现AfAlkA可有效地切除1,N(6)-乙烯腺嘌呤。我们展示了AfAlkA的高分辨率晶体结构，该结构与几个定点突变体的特征一起，为新发现的碱基切除活性提供了分子合理化解释。
相似文献
1
Structural basis for enzymatic excision of N1-methyladenine and N3-methylcytosine from DNA.从DNA中酶促切除N1-甲基腺嘌呤和N3-甲基胞嘧啶的结构基础。
EMBO J. 2007 Apr 18;26(8):2206-17. doi: 10.1038/sj.emboj.7601662. Epub 2007 Mar 29.
2
Methylpurine DNA glycosylase of the hyperthermophilic archaeon Archaeoglobus fulgidus.嗜热古菌嗜热栖热放线菌的甲基嘌呤DNA糖基化酶。
Biochemistry. 2002 Oct 22;41(42):12697-705. doi: 10.1021/bi020334w.
3
Selective base excision repair of DNA damage by the non-base-flipping DNA glycosylase AlkC.DNA 糖苷酶 AlkC 通过非碱基翻转的方式选择性修复 DNA 损伤。
EMBO J. 2018 Jan 4;37(1):63-74. doi: 10.15252/embj.201797833. Epub 2017 Oct 20.
4
Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG).人类3-甲基腺嘌呤DNA糖基化酶（AAG）对新的DNA底物文库的识别与处理
Biochemistry. 2009 Mar 10;48(9):1850-61. doi: 10.1021/bi8018898.
5
Alkylation damage in DNA and RNA--repair mechanisms and medical significance.DNA和RNA中的烷基化损伤——修复机制及医学意义
DNA Repair (Amst). 2004 Nov 2;3(11):1389-407. doi: 10.1016/j.dnarep.2004.05.004.
6
Domain structure of the DEMETER 5-methylcytosine DNA glycosylase.DEMETER 5-甲基胞嘧啶 DNA 糖基化酶的结构域。
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19225-30. doi: 10.1073/pnas.1014348107. Epub 2010 Oct 25.
7
Repair of alkylated DNA: recent advances.烷基化DNA的修复：最新进展
DNA Repair (Amst). 2007 Apr 1;6(4):429-42. doi: 10.1016/j.dnarep.2006.10.005. Epub 2006 Nov 16.
8
Crystal structures of 3-methyladenine DNA glycosylase MagIII and the recognition of alkylated bases.3-甲基腺嘌呤DNA糖基化酶MagIII的晶体结构及烷基化碱基的识别
EMBO J. 2003 Oct 1;22(19):4898-909. doi: 10.1093/emboj/cdg505.
9
The hyperthermophilic euryarchaeon Archaeoglobus fulgidus repairs uracil by single-nucleotide replacement.高温嗜热古菌 Archaeoglobus fulgidus 通过单核苷酸替换修复尿嘧啶。
J Bacteriol. 2010 Nov;192(21):5755-66. doi: 10.1128/JB.00135-10. Epub 2010 May 7.
10
AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism.阿尔克布之谜解开：通过直接逆转机制对N1-甲基腺嘌呤和N3-甲基胞嘧啶加合物进行氧化去甲基化
Trends Biochem Sci. 2003 Jan;28(1):2-5. doi: 10.1016/s0968-0004(02)00010-5.
引用本文的文献
1
Alkylated DNA repair by a novel HhH-GPD family protein from Crenarchaea.来自泉古菌的一种新型HhH-GPD家族蛋白对烷基化DNA的修复
Nucleic Acids Res. 2025 Jan 11;53(2). doi: 10.1093/nar/gkaf012.
2
Archaeal DNA alkylation repair conducted by DNA glycosylase and methyltransferase.古菌 DNA 烷基化修复由 DNA 糖苷酶和甲基转移酶执行。
Appl Microbiol Biotechnol. 2023 May;107(10):3131-3142. doi: 10.1007/s00253-023-12506-3. Epub 2023 Apr 10.
3
Characterization of a Novel Thermostable DNA Lyase Used To Prepare DNA for Next-Generation Sequencing.一种新型耐热 DNA 核酸内切酶的特性研究，用于为下一代测序准备 DNA。
Chem Res Toxicol. 2023 Feb 20;36(2):162-176. doi: 10.1021/acs.chemrestox.2c00172. Epub 2023 Jan 16.
4
Repair of Hypoxanthine in DNA Revealed by DNA Glycosylases and Endonucleases From Hyperthermophilic Archaea.嗜热古菌的DNA糖基化酶和核酸内切酶揭示的DNA中次黄嘌呤修复
Front Microbiol. 2021 Aug 31;12:736915. doi: 10.3389/fmicb.2021.736915. eCollection 2021.
5
Alleviation of C⋅C Mismatches in DNA by the Fpg Protein.Fpg蛋白对DNA中C⋅C错配的修复作用
Front Microbiol. 2021 Jun 30;12:608839. doi: 10.3389/fmicb.2021.608839. eCollection 2021.
6
Evolutionary Origins of DNA Repair Pathways: Role of Oxygen Catastrophe in the Emergence of DNA Glycosylases.DNA 修复途径的进化起源：氧危机在 DNA 糖苷酶出现中的作用。
Cells. 2021 Jun 24;10(7):1591. doi: 10.3390/cells10071591.
7
Transient kinetic analysis of oxidative dealkylation by the direct reversal DNA repair enzyme AlkB.直接逆转 DNA 修复酶 AlkB 的氧化脱烷基化的瞬态动力学分析。
J Biol Chem. 2020 May 22;295(21):7317-7326. doi: 10.1074/jbc.RA120.013517. Epub 2020 Apr 13.
8
Expansion of base excision repair compensates for a lack of DNA repair by oxidative dealkylation in budding yeast.碱基切除修复的扩展弥补了酿酒酵母中氧化脱烷基化引起的 DNA 修复缺陷。
J Biol Chem. 2019 Sep 13;294(37):13629-13637. doi: 10.1074/jbc.RA119.009813. Epub 2019 Jul 18.
9
Excision of uracil from DNA by hSMUG1 includes strand incision and processing.hSMUG1 从 DNA 中切除尿嘧啶包括链切割和加工。
Nucleic Acids Res. 2019 Jan 25;47(2):779-793. doi: 10.1093/nar/gky1184.
10
Excision of the doubly methylated base ,5-dimethylcytosine from DNA by Nei and Fpg proteins.内切酶 Nei 和 Fpg 蛋白从 DNA 中切除双甲基化碱基,5-二甲基胞嘧啶。
Philos Trans R Soc Lond B Biol Sci. 2018 Jun 5;373(1748). doi: 10.1098/rstb.2017.0337.
本文引用的文献
1
[27] Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods.[27] 用于多同晶置换和多波长反常衍射方法的最大似然重原子参数精修
Methods Enzymol. 1997;276:472-494. doi: 10.1016/S0076-6879(97)76073-7.
2
Small revisions to predicted distances around metal sites in proteins.对蛋白质中金属位点周围预测距离的微小修正。
Acta Crystallogr D Biol Crystallogr. 2006 Jun;62(Pt 6):678-82. doi: 10.1107/S0907444906014594. Epub 2006 May 12.
3
Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing 1meA and 3meC lesions in DNA.修复缺陷型小鼠研究表明，mABH2是修复DNA中1-甲基腺嘌呤（1meA）和3-甲基胞嘧啶（3meC）损伤的主要氧化脱甲基酶。
EMBO J. 2006 May 17;25(10):2189-98. doi: 10.1038/sj.emboj.7601109. Epub 2006 Apr 27.
4
AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo.AlkB在体外和体内均可逆转由脂质氧化导致的ε- DNA损伤。
Nat Struct Mol Biol. 2005 Oct;12(10):855-60. doi: 10.1038/nsmb996. Epub 2005 Oct 2.
5
Biochemical characterization and DNA repair pathway interactions of Mag1-mediated base excision repair in Schizosaccharomyces pombe.粟酒裂殖酵母中Mag1介导的碱基切除修复的生化特性及DNA修复途径相互作用
Nucleic Acids Res. 2005 Feb 18;33(3):1123-31. doi: 10.1093/nar/gki259. Print 2005.
6
Mutagenesis, genotoxicity, and repair of 1-methyladenine, 3-alkylcytosines, 1-methylguanine, and 3-methylthymine in alkB Escherichia coli.alkB大肠杆菌中1-甲基腺嘌呤、3-烷基胞嘧啶、1-甲基鸟嘌呤和3-甲基胸腺嘧啶的诱变、遗传毒性及修复
Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14051-6. doi: 10.1073/pnas.0403489101. Epub 2004 Sep 20.
7
The CCP4 suite: programs for protein crystallography.CCP4软件包：用于蛋白质晶体学的程序。
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3. doi: 10.1107/S0907444994003112.
8
The Escherichia coli 3-methyladenine DNA glycosylase AlkA has a remarkably versatile active site.大肠杆菌3-甲基腺嘌呤DNA糖基化酶AlkA具有一个极其多功能的活性位点。
J Biol Chem. 2004 Jun 25;279(26):26876-84. doi: 10.1074/jbc.M403860200. Epub 2004 May 4.
9
Repairing DNA-methylation damage.修复DNA甲基化损伤。
Nat Rev Mol Cell Biol. 2004 Feb;5(2):148-57. doi: 10.1038/nrm1312.
10
Chemical rearrangement and repair pathways of 1,N6-ethenoadenine.1,N6-乙烯腺嘌呤的化学重排与修复途径
Mutat Res. 2003 Oct 29;531(1-2):205-17. doi: 10.1016/j.mrfmmm.2003.07.007.
Zotero 插件