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

Journal article

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.

Authors: Loenarz, C; Schofield, C

• Publication status: Published
• Journal: Trends in biochemical sciences
• Volume: 36
• Issue: 1
• Pages: 7-18
• Publication date: 2011-01-01
• DOI: 10.1016/j.tibs.2010.07.002
• ISSN: 0968-0004
• Language: English
• Keywords: Collagen; Methylation; Animals; Hydroxylation; Mixed Function Oxygenases; Humans; Catalysis