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2- 氧戊二酸依赖的加氧酶。

2-Oxoglutarate-Dependent Oxygenases.

机构信息

The Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3TA, United Kingdom; email:

Current affiliation for Richard J. Hopkinson: Leicester Institute of Structural and Chemical Biology and Department of Chemistry, University of Leicester, Leicester LE1 7RH, United Kingdom; email:

出版信息

Annu Rev Biochem. 2018 Jun 20;87:585-620. doi: 10.1146/annurev-biochem-061516-044724. Epub 2018 Mar 1.

Abstract

2-Oxoglutarate (2OG)-dependent oxygenases (2OGXs) catalyze a remarkably diverse range of oxidative reactions. In animals, these comprise hydroxylations and N-demethylations proceeding via hydroxylation; in plants and microbes, they catalyze a wider range including ring formations, rearrangements, desaturations, and halogenations. The catalytic flexibility of 2OGXs is reflected in their biological functions. After pioneering work identified the roles of 2OGXs in collagen biosynthesis, research revealed they also function in plant and animal development, transcriptional regulation, nucleic acid modification/repair, fatty acid metabolism, and secondary metabolite biosynthesis, including of medicinally important antibiotics. In plants, 2OGXs are important agrochemical targets and catalyze herbicide degradation. Human 2OGXs, particularly those regulating transcription, are current therapeutic targets for anemia and cancer. Here, we give an overview of the biochemistry of 2OGXs, providing examples linking to biological function, and outline how knowledge of their enzymology is being exploited in medicine, agrochemistry, and biocatalysis.

摘要

2-氧代戊二酸(2OG)依赖性加氧酶(2OGXs)催化范围广泛的氧化反应。在动物中,这些包括通过羟化作用进行的羟化和 N-去甲基化;在植物和微生物中,它们催化范围更广,包括环形成、重排、去饱和和卤化。2OGXs 的催化灵活性反映在它们的生物学功能上。在开创性工作确定了 2OGXs 在胶原蛋白生物合成中的作用后,研究表明它们还在植物和动物发育、转录调控、核酸修饰/修复、脂肪酸代谢和次生代谢物生物合成中发挥作用,包括具有重要药用价值的抗生素。在植物中,2OGXs 是重要的农用化学品靶标,可催化除草剂降解。人类 2OGXs,特别是那些调节转录的 2OGXs,是目前治疗贫血和癌症的治疗靶点。在这里,我们概述了 2OGXs 的生物化学,提供了将其与生物学功能联系起来的例子,并概述了它们的酶学知识如何在医学、农用化学和生物催化中得到利用。

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