Cited by 274Metal-Catalyzed Oxygenation MechanismsCancer-related gene regulationCancer, Hypoxia, and Metabolism

Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases

Loenarz, Christoph, Schofield, Christopher J.·2011·Trends in Biochemical Sciences

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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Crossref · 10.1016/j.tibs.2010.07.002

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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].”

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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

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