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对氧磷酶-1的分子结构及其与酶活性和生物学功能相关的修饰——综述

Molecular Structure of Paraoxonase-1 and Its Modifications in Relation to Enzyme Activity and Biological Functions-A Comprehensive Review.

作者信息

Lewoń-Mrozek Dominika, Kurzynoga Julia, Jędrzejewski Piotr, Kędzierska Karolina, Partyka Alicja, Kuriata-Kordek Magdalena, Ściskalska Milena

机构信息

Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Rudolfa Weigla 12 St., 53-114 Wroclaw, Poland.

Student Society of Laboratory Diagnosticians, Wroclaw Medical University, Borowska 211A St., 50-556 Wroclaw, Poland.

出版信息

Int J Mol Sci. 2024 Dec 6;25(23):13129. doi: 10.3390/ijms252313129.

DOI:10.3390/ijms252313129
PMID:39684839
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11642642/
Abstract

PON1 is a Ca-dependent enzyme that indicates a hydrolytic activity towards a broad spectrum of substrates. The mechanism of hydrolysis catalyzed by this enzyme is poorly understood. It was shown that the active site of PON1 is highly dynamic. The catalytic center of this enzyme consists of side chains of amino acids binding two calcium ions, from which the first one performs a structural function and the other one is responsible for the catalytic properties of PON1. This review summarizes available information on the structure of PONs, the role of amino acids located in the active site in specificity, and multiple substrate affinity of enzymes for understanding and explaining the basis of the physiological function of PONs. Moreover, in this paper, we described the changes in the structure of PONs induced by environmental and genetic factors and their association with diseases. The detoxification efficiency depends on the polymorphism of the gene, especially Q192R. However, data on the association between single-nucleotide polymorphisms (SNPs) in the gene and cardiovascular or neurodegenerative diseases are insufficient. The reviewed papers may confirm that PON1 is a very promising tool for diagnostics, but further studies are required.

摘要

对氧磷酶1(PON1)是一种钙依赖性酶,对多种底物具有水解活性。人们对该酶催化水解的机制了解甚少。研究表明,PON1的活性位点具有高度动态性。该酶的催化中心由结合两个钙离子的氨基酸侧链组成,其中第一个钙离子起结构作用,另一个钙离子负责PON1的催化特性。本综述总结了有关对氧磷酶(PONs)结构、活性位点氨基酸在特异性方面的作用以及酶对多种底物的亲和力的现有信息,以理解和解释PONs生理功能的基础。此外,在本文中,我们描述了环境和遗传因素引起的PONs结构变化及其与疾病的关联。解毒效率取决于该基因的多态性,尤其是Q192R。然而,关于该基因单核苷酸多态性(SNP)与心血管疾病或神经退行性疾病之间关联的数据并不充分。所综述的论文可能证实PON1是一种非常有前景的诊断工具,但仍需要进一步研究。

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Molecular Structure of Paraoxonase-1 and Its Modifications in Relation to Enzyme Activity and Biological Functions-A Comprehensive Review.对氧磷酶-1的分子结构及其与酶活性和生物学功能相关的修饰——综述
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J Cancer Res Clin Oncol. 2025 Aug 12;151(8):229. doi: 10.1007/s00432-025-06282-y.
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PON-1 and PON-2 Polymorphisms and PON-1 Paraoxonase Activity in People Living with HIV-1.

本文引用的文献

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The association of the paraoxonase 1 Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD.伊朗疑似冠心病患者中对氧磷酶1 Q192R多态性与冠心病(CAD)及心脏代谢危险因素的关联。
Front Cardiovasc Med. 2023 Jan 9;9:1037940. doi: 10.3389/fcvm.2022.1037940. eCollection 2022.
2
Paraoxonase Role in Human Neurodegenerative Diseases.对氧磷酶在人类神经退行性疾病中的作用。
Antioxidants (Basel). 2020 Dec 24;10(1):11. doi: 10.3390/antiox10010011.
3
The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3.
HIV-1感染者的对氧磷酶-1(PON-1)和对氧磷酶-2(PON-2)基因多态性及PON-1对氧磷酶活性
Antioxidants (Basel). 2025 Feb 12;14(2):209. doi: 10.3390/antiox14020209.
对氧磷酶 1 的结构与功能及其与对氧磷酶 2 和 3 的比较。
Molecules. 2020 Dec 17;25(24):5980. doi: 10.3390/molecules25245980.
4
HDL Proteome and Alzheimer's Disease: Evidence of a Link.高密度脂蛋白蛋白质组与阿尔茨海默病:存在关联的证据。
Antioxidants (Basel). 2020 Dec 3;9(12):1224. doi: 10.3390/antiox9121224.
5
Toxicity assessment due to prenatal and lactational exposure to lead, cadmium and mercury mixtures.产前和哺乳期暴露于铅、镉和汞混合物的毒性评估。
Environ Int. 2019 Dec;133(Pt B):105192. doi: 10.1016/j.envint.2019.105192. Epub 2019 Oct 19.
6
Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery.接受冠状动脉手术患者的对氧磷酶1活性、多态性与动脉粥样硬化危险因素
J Clin Med. 2019 Mar 30;8(4):441. doi: 10.3390/jcm8040441.
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PON1 is a disease modifier gene in amyotrophic lateral sclerosis: association of the Q192R polymorphism with bulbar onset and reduced survival.PON1 是肌萎缩侧索硬化症的疾病修饰基因:Q192R 多态性与球部起病和生存时间缩短相关。
Neurol Sci. 2019 Jul;40(7):1469-1473. doi: 10.1007/s10072-019-03834-2. Epub 2019 Mar 22.
8
Associations of the PON1 rs662 polymorphism with circulating oxidized low-density lipoprotein and lipid levels: a systematic review and meta-analysis.PON1 rs662 多态性与循环氧化型低密度脂蛋白和血脂水平的关联:系统评价和荟萃分析。
Lipids Health Dis. 2018 Dec 13;17(1):281. doi: 10.1186/s12944-018-0937-8.
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