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Expanding chemical biology of 2-oxoglutarate oxygenases

Abstract

Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate–dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a multiplicity of histone modifications has some analogy with their role in enabling structural diversity in secondary metabolism.

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Figure 1: Known and proposed roles for human 2OG oxygenases with outline catalytic cycle.
Figure 2: Overall folds and active sites of human 2OG oxygenases.
Figure 3: The combinatorial and dynamic nature of covalent modifications to the histone H3 N terminus, highlighting the role of 2OG oxygenases, and their role in introducing diversity into peptide-derived secondary metabolites.

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Acknowledgements

We thank the Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the Rhodes Trust (C.L.) for funding.

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C.J.S. is a cofounder of ReOx, a company that aims to exploit scientific discoveries on the hypoxic response for medicinal use.

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Loenarz, C., Schofield, C. Expanding chemical biology of 2-oxoglutarate oxygenases. Nat Chem Biol 4, 152–156 (2008). https://doi.org/10.1038/nchembio0308-152

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