Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl hydroxylase JMJD6.
Lysyl and prolyl hydroxylations are well-known post-translational modifications to animal and plant proteins with extracellular roles. More recent work has indicated that the hydroxylation of intracellular animal proteins may be common. JMJD6 catalyses the iron- and 2-oxoglutarate-dependent hydroxylation of lysyl residues in arginine-serine-rich domains of RNA splicing-related proteins. We report crystallographic studies on the catalytic domain of JMJD6 in complex with Ni(II) substituting for Fe(II). Together with mutational studies, the structural data suggest how JMJD6 binds its lysyl residues such that it can catalyse C-5 hydroxylation rather than Nepsilon-demethylation, as for analogous enzymes.
Mantri
Monica
M
Department of Chemistry and Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
Krojer
Tobias
T
Bagg
Eleanor A
EA
Webby
Celia J
CJ
Butler
Danica S
DS
Kochan
Grazyna
G
Kavanagh
Kathryn L
KL
Oppermann
Udo
U
McDonough
Michael A
MA
Schofield
Christopher J
CJ
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009532:Nickel / Q000378:metabolism; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D017931:DNA Primers; D007656:Ketoglutaric Acids; D050505:Mutant Proteins; D011994:Recombinant Proteins; D009532:Nickel; D007501:Iron; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase