2-Oxoglutarate-Dependent Oxygenases

被引:314
作者
Islam, Md. Saiful [1 ]
Leissing, Thomas M. [1 ]
Chowdhury, Rasheduzzaman [1 ]
Hopkinson, Richard J. [1 ,2 ,3 ]
Schofield, Christopher J. [1 ]
机构
[1] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England
[2] Univ Leicester, Leicester Inst Struct & Chem Biol, Leicester LE1 7RH, Leics, England
[3] Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, England
来源
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 87 | 2018年 / 87卷
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
2-oxoglutarate; alpha-ketoglutarate; oxygenase; dioxygenase; hydroxylation; demethylation; biosynthesis; oxygen sensing; hypoxia; epigenetics; HYPOXIA-INDUCIBLE FACTOR; GAMMA-BUTYROBETAINE HYDROXYLASE; FACTOR HIF PROLYL; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BETA-HYDROXYLATION; ESCHERICHIA-COLI; NONHEME IRON; 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID; ONCOMETABOLITE; 2-HYDROXYGLUTARATE;
D O I
10.1146/annurev-biochem-061516-044724
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:585 / 620
页数:36
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