2-Oxoglutarate-Dependent Oxygenases

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, d...

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Bibliographic Details
Published in:Annual review of biochemistry 2018-06, Vol.87 (1), p.585-620
Main Authors: Islam, Md. Saiful, Leissing, Thomas M, Chowdhury, Rasheduzzaman, Hopkinson, Richard J, Schofield, Christopher J
Format: Article
Language:English
Subjects:
2-oxoglutarate
Acids
Agrochemicals
Anemia
Animals
Antibiotics
Biocatalysis
Biosynthesis
Cancer
Catalysis
Catalysts
Chemical reactions
Collagen
Collagen - biosynthesis
demethylation
dioxygenase
Enzymes
Enzymology
epigenetics
Gene regulation
Humans
Hydroxylation
hypoxia
Ketoglutaric acid
Ketoglutaric Acids - metabolism
Medicinal plants
Metabolism
Metabolites
Models, Biological
Models, Molecular
Nucleic acids
Oxidation-Reduction
oxygen sensing
oxygenase
Oxygenases - chemistry
Oxygenases - metabolism
Plants (botany)
Protein Conformation
Studies
Substrate Specificity
Therapeutic applications
Transcription
α-ketoglutarate
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Summary: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.
ISSN:0066-4154
1545-4509
DOI:10.1146/annurev-biochem-061516-044724