用合成的过渡态类似物对碱基切除修复糖苷酶进行剖析。
Profiling base excision repair glycosylases with synthesized transition state analogs.
机构信息
Department of Chemistry, University of California, Davis, Building 143, One Shields Avenue, Davis, CA 95616, United States.
出版信息
Bioorg Med Chem Lett. 2011 Sep 1;21(17):4969-72. doi: 10.1016/j.bmcl.2011.05.085. Epub 2011 May 30.
Abstract
Two base excision repair glycosylase (BER) transition state (TS) mimics, (3R,4R)-1-benzyl (hydroxymethyl) pyrrolidin-3-ol (1NBn) and (3R,4R)-(hydroxymethyl) pyrrolidin-3-ol (1N), were synthesized using an improved method. Several BER glycosylases that repair oxidized DNA bases, bacterial formamidopyrimdine glycosylase (Fpg), human OG glycosylase (hOGG1) and human Nei-like glycosylase 1 (hNEIL1) exhibit exceptionally high affinity (K(d)∼pM) with DNA duplexes containing the 1NBn and 1N nucleotide. Notably, comparison of the K(d) values of both TS mimics relative to an abasic analog (THF) in duplex contexts paired opposite C or A suggest that these DNA repair enzymes use distinctly different mechanisms for damaged base recognition and catalysis despite having overlapping substrate specificities.
摘要
两种碱基切除修复糖苷酶（BER）过渡态（TS）模拟物，（3R，4R）-1-苄基（羟甲基）吡咯烷-3-醇（1NBn）和（3R，4R）-（羟甲基）吡咯烷-3-醇（1N），使用改进的方法合成。几种修复氧化 DNA 碱基的 BER 糖苷酶，如细菌的 formamidopyrimdine 糖苷酶（Fpg）、人 OG 糖苷酶（hOGG1）和人 Nei 样糖苷酶 1（hNEIL1），与含有 1NBn 和 1N 核苷酸的 DNA 双链体表现出极高的亲和力（Kd∼pM）。值得注意的是，将这两种 TS 模拟物的 Kd 值与在双链体背景下配对 C 或 A 的无碱基类似物（THF）进行比较表明，尽管这些 DNA 修复酶具有重叠的底物特异性，但它们使用截然不同的机制来识别和催化受损碱基。
相似文献
1
Profiling base excision repair glycosylases with synthesized transition state analogs.用合成的过渡态类似物对碱基切除修复糖苷酶进行剖析。
Bioorg Med Chem Lett. 2011 Sep 1;21(17):4969-72. doi: 10.1016/j.bmcl.2011.05.085. Epub 2011 May 30.
2
Targeting Base Excision Repair Glycosylases with DNA Containing Transition State Mimics Prepared via Click Chemistry.通过点击化学制备含有过渡态模拟物的 DNA 靶向碱基切除修复糖苷酶。
ACS Chem Biol. 2019 Jan 18;14(1):27-36. doi: 10.1021/acschembio.8b00771. Epub 2019 Jan 2.
3
Surprising repair activities of nonpolar analogs of 8-oxoG expose features of recognition and catalysis by base excision repair glycosylases.非极性 8-oxoG 类似物的惊人修复活性揭示了碱基切除修复糖苷酶的识别和催化特征。
J Am Chem Soc. 2012 Jan 25;134(3):1653-61. doi: 10.1021/ja208510m. Epub 2012 Jan 9.
4
Recognition and removal of oxidized guanines in duplex DNA by the base excision repair enzymes hOGG1, yOGG1, and yOGG2.碱基切除修复酶hOGG1、yOGG1和yOGG2对双链DNA中氧化鸟嘌呤的识别与去除
Biochemistry. 2003 Sep 30;42(38):11373-81. doi: 10.1021/bi034951b.
5
Energetics of lesion recognition by a DNA repair protein: thermodynamic characterization of formamidopyrimidine-glycosylase (Fpg) interactions with damaged DNA duplexes.一种DNA修复蛋白识别损伤的能量学：甲酰胺嘧啶糖基化酶（Fpg）与受损DNA双链体相互作用的热力学特征
J Mol Biol. 2003 May 16;328(5):1047-60. doi: 10.1016/s0022-2836(03)00365-6.
6
Superior removal of hydantoin lesions relative to other oxidized bases by the human DNA glycosylase hNEIL1.相较于其他氧化碱基，人类DNA糖基化酶hNEIL1对乙内酰脲损伤具有更高效的去除能力。
Biochemistry. 2008 Jul 8;47(27):7137-46. doi: 10.1021/bi800160s. Epub 2008 Jun 11.
7
2'-Fluorinated Hydantoins as Chemical Biology Tools for Base Excision Repair Glycosylases.2'-氟代海因类作为碱基切除修复糖苷酶的化学生物学工具。
ACS Chem Biol. 2020 Apr 17;15(4):915-924. doi: 10.1021/acschembio.9b00923. Epub 2020 Mar 13.
8
Human DNA glycosylases involved in the repair of oxidatively damaged DNA.参与氧化损伤DNA修复的人类DNA糖基化酶。
Biol Pharm Bull. 2004 Apr;27(4):480-5. doi: 10.1248/bpb.27.480.
9
The role of the N-terminal domain of human apurinic/apyrimidinic endonuclease 1, APE1, in DNA glycosylase stimulation.人脱嘌呤/脱嘧啶核酸内切酶 1（APE1）N 端结构域在 DNA 糖基化酶激活中的作用。
DNA Repair (Amst). 2018 Apr;64:10-25. doi: 10.1016/j.dnarep.2018.02.001. Epub 2018 Feb 11.
10
High resolution characterization of formamidopyrimidine-DNA glycosylase interaction with its substrate by chemical cross-linking and mass spectrometry using substrate analogs.通过化学交联和使用底物类似物的质谱法对甲酰胺嘧啶-DNA糖基化酶与其底物的相互作用进行高分辨率表征。
J Biol Chem. 2006 Oct 27;281(43):32353-65. doi: 10.1074/jbc.M606217200. Epub 2006 Aug 22.
引用本文的文献
1
Structure of human MUTYH and functional profiling of cancer-associated variants reveal an allosteric network between its [4Fe-4S] cluster cofactor and active site required for DNA repair.人类MUTYH的结构及癌症相关变体的功能分析揭示了其[4Fe-4S]簇辅因子与DNA修复所需活性位点之间的变构网络。
Nat Commun. 2025 Apr 16;16(1):3596. doi: 10.1038/s41467-025-58361-w.
2
Structural snapshots of base excision by the cancer-associated variant MutY N146S reveal a retaining mechanism.癌症相关突变体 MutY N146S 的碱基切除结构快照揭示了一种保留机制。
Nucleic Acids Res. 2023 Feb 22;51(3):1034-1049. doi: 10.1093/nar/gkac1246.
3
Recognition of a Clickable Abasic Site Analog by DNA Polymerases and DNA Repair Enzymes.DNA 聚合酶和 DNA 修复酶对可点击无碱基位点类似物的识别。
Int J Mol Sci. 2022 Nov 1;23(21):13353. doi: 10.3390/ijms232113353.
4
Structural Insights into the Mechanism of Base Excision by MBD4.MBD4 碱基切除修复的结构机制研究
J Mol Biol. 2021 Jul 23;433(15):167097. doi: 10.1016/j.jmb.2021.167097. Epub 2021 Jun 6.
5
Structural Basis for Finding OG Lesions and Avoiding Undamaged G by the DNA Glycosylase MutY.MutY 碱基糖苷酶发现 OG 损伤和避免未损伤 G 的结构基础
ACS Chem Biol. 2020 Jan 17;15(1):93-102. doi: 10.1021/acschembio.9b00639. Epub 2019 Dec 27.
6
Targeting Base Excision Repair Glycosylases with DNA Containing Transition State Mimics Prepared via Click Chemistry.通过点击化学制备含有过渡态模拟物的 DNA 靶向碱基切除修复糖苷酶。
ACS Chem Biol. 2019 Jan 18;14(1):27-36. doi: 10.1021/acschembio.8b00771. Epub 2019 Jan 2.
7
Fe-S Clusters and MutY Base Excision Repair Glycosylases: Purification, Kinetics, and DNA Affinity Measurements.铁硫簇与MutY碱基切除修复糖基化酶：纯化、动力学及DNA亲和力测定
Methods Enzymol. 2018;599:21-68. doi: 10.1016/bs.mie.2017.11.035. Epub 2018 Jan 10.
8
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.
9
Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases.碱基切除修复糖基化酶MutY的结构与立体化学揭示了一种类似于保留型糖苷酶的机制。
Nucleic Acids Res. 2016 Jan 29;44(2):801-10. doi: 10.1093/nar/gkv1469. Epub 2015 Dec 15.
10
The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions.DNA糖基化酶AlkD采用非碱基翻转机制切除大的损伤。
Nature. 2015 Nov 12;527(7577):254-8. doi: 10.1038/nature15728. Epub 2015 Oct 28.
本文引用的文献
1
Ultrasensitive in situ visualization of active glucocerebrosidase molecules.超敏原位可视化活性葡萄糖脑苷脂酶分子。
Nat Chem Biol. 2010 Dec;6(12):907-13. doi: 10.1038/nchembio.466. Epub 2010 Oct 31.
2
Asymmetric total synthesis of 1-deoxy-7,8-di-epi-castanospermine.1-脱氧-7,8-二-表-苦参碱的不对称全合成。
Org Biomol Chem. 2010 Apr 7;8(7):1725-30. doi: 10.1039/b924721a. Epub 2010 Feb 9.
3
Transition state analogues rescue ribosomes from saporin-L1 ribosome inactivating protein.过渡态类似物可从皂草素-L1核糖体失活蛋白中拯救核糖体。
Biochemistry. 2009 Oct 20;48(41):9941-8. doi: 10.1021/bi901425h.
4
Mechanistic insights into glycosidase chemistry.糖苷酶化学的机理洞察
Curr Opin Chem Biol. 2008 Oct;12(5):539-55. doi: 10.1016/j.cbpa.2008.05.010.
5
Superior removal of hydantoin lesions relative to other oxidized bases by the human DNA glycosylase hNEIL1.相较于其他氧化碱基，人类DNA糖基化酶hNEIL1对乙内酰脲损伤具有更高效的去除能力。
Biochemistry. 2008 Jul 8;47(27):7137-46. doi: 10.1021/bi800160s. Epub 2008 Jun 11.
6
Transition-state analysis of the DNA repair enzyme MutY.DNA修复酶MutY的过渡态分析
J Am Chem Soc. 2008 Apr 30;130(17):5789-97. doi: 10.1021/ja711363s. Epub 2008 Apr 5.
7
Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases.8-氧代鸟嘌呤糖基化酶对甲酰胺基嘧啶的高效去除作用
Biochemistry. 2008 Jan 22;47(3):1043-50. doi: 10.1021/bi701619u. Epub 2007 Dec 23.
8
A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine.氮杂螺吡喃衍生物和 (1S,8aR)-1-羟基吲哚里西啶的发散不对称方法。
Beilstein J Org Chem. 2007 Nov 8;3:41. doi: 10.1186/1860-5397-3-41.
9
Chemical-biological fingerprinting: probing the properties of DNA lesions formed by peroxynitrite.化学生物指纹图谱：探究过氧亚硝酸根形成的DNA损伤的性质
Chem Res Toxicol. 2007 Nov;20(11):1718-29. doi: 10.1021/tx700273u. Epub 2007 Oct 18.
10
A practical synthesis of (3R,4R)-N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol.(3R,4R)-N-叔丁氧羰基-4-羟甲基吡咯烷-3-醇的实用合成方法
Org Biomol Chem. 2007 Sep 7;5(17):2800-2. doi: 10.1039/b708796a. Epub 2007 Jul 20.
Zotero 插件