Human UTY(KDM6C) is a male-specific nϵ-methyl lysyl demethylase

DOI: 10.1074/jbc.M114.555052
PMID: 24798337

Authors: Louise J. Walport (University of Oxford) , Richard J. Hopkinson (University of Oxford) , Melanie Vollmar (Structural Genomics Consortium, University of Oxford) , Sarah K. Madden (University of Oxford) , Carina Gileadi (Structural Genomics Consortium, University of Oxford) , U. Oppermann (Structural Genomics Consortium, University of Oxford) , Christopher J. Schofield (Chemistry Research Laboratory, Department of Chemistry, University of Oxford, U.K.) , Catrine Johansson (Structural Genomics Consortium, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry , VOL 289 (26) , PAGES 18302 - 18313

State: Published (Approved)
Published: June 2014
Diamond Proposal Number(s): 8421

Abstract: The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N?-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochemical studies, employing MS and NMR, that UTY(KDM6C) is an active KDM. Crystallographic analyses reveal that the UTY(KDM6C) active site is highly conserved with those of KDM6B and KDM6A. UTY(KDM6C) catalyzes demethylation of H3K27 peptides in vitro, analogously to KDM6B and KDM6A, but with reduced activity, due to point substitutions involved in substrate binding. The results expand the set of human KDMs and will be of use in developing selective KDM inhibitors.

Journal Keywords: Crystallography; X-Ray; Histones; Humans; Lysine; Male; Methylation; Models; Molecular; Nuclear; Protein; Tertiary; Sequence; Species Specificity

Subject Areas: Biology and Bio-materials, Medicine, Chemistry


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 30/09/2014 09:19

Documents:
1-s2.0-S0021925820405393-main.pdf

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)