Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases
Abstract
Pioneering work in the 1960s defined prolyl and lysyl hydroxylations as physiologically important oxygenase-catalyzed modifications in collagen biosynthesis; subsequent studies demonstrated that extracellular epidermal growth factor-like domains were hydroxylated at aspartyl and asparaginyl residues. More recent work on the hypoxia-sensing mechanism in animals has shown that prolyl and asparaginyl hydroxylation of the hypoxia-inducible transcription factor play central roles in sensing hypoxia, by regulating protein-protein interactions in an oxygen-dependent manner. The collective results imply that protein hydroxylation is more common than previously perceived. Most protein hydroxylases employ Fe(II) as a cofactor, and 2-oxoglutarate and oxygen as co-substrates. Related enzymes catalyze the demethylation of N(ɛ)-methyl lysine residues in histones and of N-methylated nucleic acids, as well as hydroxylation of 5-methyl cytosine in DNA and 5-methoxycarbonylmethyluridine at the wobble position of tRNA. The combination of new molecular biological and analytical techniques is likely to reveal further roles for oxygenase-mediated modifications to biomacromolecules.
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The largest group of enzymes using vitamin C as a cofactor is the iron-dependent and 2-oxoglutarate-dependent dioxygenases superfamily (2OGO), representing about 80 enzymes in humans responsible for modification of important biological substances and processes.
“The largest group of enzymes using vitamin C as one of their cofactors is the iron-dependent and 2-oxoglutarate-dependent dioxygenases superfamily (2OGO, α-ketoglutarate-dependent hydroxylases). In humans, it represents about 80 enzymes responsible for the modification of important biological substances and processes (Table 2) [97,98,99].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [99]
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- Authors
- Loenarz, C., & Schofield, C. J.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Schofield, Christopher J.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 36
- Issue
- 1
- Pages
- 7-18
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2087161387
- Cited by
- 274
- References
- 96
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 19 · 2023: 13 · 2022: 19 · 2021: 14 · 2020: 18 · 2019: 10 · 2018: 17 · 2017: 28 · 2016: 17 · 2015: 24 · 2014: 32 · 2013: 23 · 2012: 12
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Cancer Research UK
- Research Councils UK
- Rhodes Scholarships
- European Commission
- Biotechnology and Biological Sciences Research Council (BB/D011523/1, BB/F006349/1)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- protein hydroxylation, prolyl hydroxylation, lysyl hydroxylation, collagen synthesis, hypoxia-inducible factor, hypoxia sensing, histone demethylation
- MeSH terms
- Animals, Catalysis, Collagen, Humans, Mixed Function Oxygenases, Hydroxylation, Methylation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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