Structure-function relationships of human JmjC oxygenases-demethylases versus hydroxylases.
The Jumonji-C (JmjC) subfamily of 2-oxoglutarate (2OG)-dependent oxygenases are of biomedical interest because of their roles in the regulation of gene expression and protein biosynthesis. Human JmjC 2OG oxygenases catalyze oxidative modifications to give either chemically stable alcohol products, or in the case of Nɛ-methyl lysine demethylation, relatively unstable hemiaminals that fragment to give formaldehyde and the demethylated product. Recent work has yielded conflicting reports as to whether some JmjC oxygenases catalyze N-methyl group demethylation or hydroxylation reactions. We review JmjC oxygenase-catalyzed reactions within the context of structural knowledge, highlighting key differences between hydroxylases and demethylases, which have the potential to inform on the possible type(s) of reactions catalyzed by partially characterized or un-characterized JmjC oxygenases in humans and other organisms.
Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Suzana
S
Markolovic
Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK; Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Old Road Campus, University of Oxford, Headington, Oxford OX3 7DQ, UK.
Thomas M
TM
Leissing
Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Rasheduzzaman
R
Chowdhury
Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Sarah E
SE
Wilkins
Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Old Road Campus, University of Oxford, Headington, Oxford OX3 7DQ, UK.
Xin
X
Lu
Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK. Electronic address: christopher.schofield@chem.ox.ac.uk.
Christopher J
CJ
Schofield
D000818:Animals; D055162:Biocatalysis; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D055503:Protein Multimerization; D013329:Structure-Activity Relationship
D006899:Mixed Function Oxygenases; D056484:Jumonji Domain-Containing Histone Demethylases