可水解单宁是一种铁螯合剂，可抑制 DNA 修复酶 ALKBH2。
Hydrolyzable Tannins Are Iron Chelators That Inhibit DNA Repair Enzyme ALKBH2.
机构信息
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy , University of Rhode Island , Kingston , Rhode Island 02881 , United States.
出版信息
Chem Res Toxicol. 2019 Jun 17;32(6):1082-1086. doi: 10.1021/acs.chemrestox.8b00398. Epub 2019 May 28.
Abstract
Hydrolyzable tannins are a class of polyphenolic compounds commonly found in natural products. In this work, we studied the in vitro inhibitory mechanism of six molecules in this class on ALKBH2, an Fe(II)/α-ketoglutarate-dependent DNA repair enzyme in the AlkB family. We determined the IC values of these compounds on the repair of 3-methylcytosine and 1-methyladenine, the prototypical substrates of ALKBH2. A structure-activity relationship was also observed between the strength of inhibition and the number of galloyl moieties in a molecule. In addition, we found that the inhibition by this class of polyphenolic compounds on ALKBH2 is through an iron-chelating mechanism.
摘要
可水解单宁是一类常见于天然产物的多酚化合物。在这项工作中，我们研究了该类的 6 种分子对 AlkB 家族中的 Fe(II)/α-酮戊二酸依赖性 DNA 修复酶 ALKBH2 的体外抑制机制。我们测定了这些化合物对 ALKBH2 修复 3-甲基胞嘧啶和 1-甲基腺嘌呤这两种典型底物的抑制常数（IC 值）。我们还观察到，抑制强度与分子中没食子酰基的数量之间存在结构-活性关系。此外，我们发现该类多酚化合物对 ALKBH2 的抑制作用是通过铁螯合机制实现的。
相似文献
1
Hydrolyzable Tannins Are Iron Chelators That Inhibit DNA Repair Enzyme ALKBH2.
Chem Res Toxicol. 2019 Jun 17;32(6):1082-1086. doi: 10.1021/acs.chemrestox.8b00398. Epub 2019 May 28.
2
Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage.
J Biol Chem. 2016 May 20;291(21):11083-93. doi: 10.1074/jbc.M115.711895. Epub 2016 Mar 25.
3
Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions.
Chem Res Toxicol. 2017 Apr 17;30(4):1102-1110. doi: 10.1021/acs.chemrestox.7b00009. Epub 2017 Mar 24.
4
DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro.
Nucleic Acids Res. 2019 Jun 20;47(11):5522-5529. doi: 10.1093/nar/gkz395.
5
Insights into the Direct Oxidative Repair of Etheno Lesions: MD and QM/MM Study on the Substrate Scope of ALKBH2 and AlkB.
DNA Repair (Amst). 2020 Dec;96:102944. doi: 10.1016/j.dnarep.2020.102944. Epub 2020 Sep 9.
6
Interactions between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study.
Mol Divers. 2023 Apr;27(2):931-938. doi: 10.1007/s11030-022-10444-2. Epub 2022 May 11.
7
Inhibition of human DNA alkylation damage repair enzyme ALKBH2 by HIV protease inhibitor ritonavir.
DNA Repair (Amst). 2024 Sep;141:103732. doi: 10.1016/j.dnarep.2024.103732. Epub 2024 Jul 25.
8
Lack of mismatch repair enhances resistance to methylating agents for cells deficient in oxidative demethylation.
J Biol Chem. 2024 Aug;300(8):107492. doi: 10.1016/j.jbc.2024.107492. Epub 2024 Jun 24.
9
The DNA dioxygenase ALKBH2 protects Arabidopsis thaliana against methylation damage.
Nucleic Acids Res. 2012 Aug;40(14):6620-31. doi: 10.1093/nar/gks327. Epub 2012 Apr 24.
10
Conformational Dynamics of Human ALKBH2 Dioxygenase in the Course of DNA Repair as Revealed by Stopped-Flow Fluorescence Spectroscopy.
Molecules. 2022 Aug 4;27(15):4960. doi: 10.3390/molecules27154960.
引用本文的文献
1
Neuroprotective effects of tannic acid in the postischemic brain via direct chelation of Zn.
Anim Cells Syst (Seoul). 2022 Aug 19;26(4):183-191. doi: 10.1080/19768354.2022.2113915. eCollection 2022.
2
Isolation and Characterization of Galloylglucoses Effective against Multidrug-Resistant Strains of and .
Molecules. 2022 Aug 8;27(15):5045. doi: 10.3390/molecules27155045.
3
Boosting 5-ALA-based photodynamic therapy by a liposomal nanomedicine through intracellular iron ion regulation.
Acta Pharm Sin B. 2021 May;11(5):1329-1340. doi: 10.1016/j.apsb.2021.03.017. Epub 2021 Apr 29.
4
Antiviral Role of Phenolic Compounds against Dengue Virus: A Review.
Biomolecules. 2020 Dec 24;11(1):11. doi: 10.3390/biom11010011.
5
Genome-Protecting Compounds as Potential Geroprotectors.
Int J Mol Sci. 2020 Jun 24;21(12):4484. doi: 10.3390/ijms21124484.
本文引用的文献
1
A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.
Environ Toxicol. 2018 May;33(5):603-618. doi: 10.1002/tox.22549. Epub 2018 Feb 15.
2
Tannic acid (TA): A molecular tool for chelating and imaging labile iron.
Eur J Pharm Sci. 2018 Mar 1;114:64-73. doi: 10.1016/j.ejps.2017.12.004. Epub 2017 Dec 7.
3
Characterization of Byproducts from Chemical Syntheses of Oligonucleotides Containing 1-Methyladenine and 3-Methylcytosine.
ACS Omega. 2017 Nov 30;2(11):8205-8212. doi: 10.1021/acsomega.7b01482. Epub 2017 Nov 20.
4
Copper Inhibits the AlkB Family DNA Repair Enzymes under Wilson's Disease Condition.
Chem Res Toxicol. 2017 Oct 16;30(10):1794-1796. doi: 10.1021/acs.chemrestox.7b00230. Epub 2017 Sep 26.
5
Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions.
Chem Res Toxicol. 2017 Apr 17;30(4):1102-1110. doi: 10.1021/acs.chemrestox.7b00009. Epub 2017 Mar 24.
6
Glucitol-core containing gallotannins inhibit the formation of advanced glycation end-products mediated by their antioxidant potential.
Food Funct. 2016 May 18;7(5):2213-22. doi: 10.1039/c6fo00169f. Epub 2016 Apr 22.
7
Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage.
J Biol Chem. 2016 May 20;291(21):11083-93. doi: 10.1074/jbc.M115.711895. Epub 2016 Mar 25.
8
Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA.
Chem Res Toxicol. 2016 Apr 18;29(4):687-93. doi: 10.1021/acs.chemrestox.5b00522. Epub 2016 Mar 15.
9
Metal chelation, radical scavenging and inhibition of Aβ₄₂ fibrillation by food constituents in relation to Alzheimer's disease.
Food Chem. 2016 May 15;199:185-94. doi: 10.1016/j.foodchem.2015.11.118. Epub 2015 Nov 26.
10
Pomegranate's Neuroprotective Effects against Alzheimer's Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites.
ACS Chem Neurosci. 2016 Jan 20;7(1):26-33. doi: 10.1021/acschemneuro.5b00260. Epub 2015 Nov 17.
Zotero 插件