3ZLI

Crystal structure of JmjC domain of human histone demethylase UTY

Summary for 3ZLI

• Entry DOI: 10.2210/pdb3zli/pdb
• Related: 3ZPO
• Descriptor: HISTONE DEMETHYLASE UTY, 1,2-ETHANEDIOL, 2-OXOGLUTARIC ACID, ... (6 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 111416.46

Authors

Vollmar, M.,Gileadi, C.,Shrestha, L.,Goubin, S.,Johansson, C.,Krojer, T.,Raynor, J.W.,Bradley, A.,von Delft, F.,Arrowsmith, C.H.,Bountra, C.,Edwards, A.,Oppermann, U. (deposition date: 2013-01-31, release date: 2013-02-27, Last modification date: 2023-12-20)

Primary citation

Walport, L.J.,Hopkinson, R.J.,Vollmar, M.,Madden, S.K.,Gileadi, C.,Oppermann, U.,Schofield, C.J.,Johansson, C.
Human Uty(Kdm6C) is a Male-Specific Nepsilon-Methyl Lysyl Demethylase.
J.Biol.Chem., 289:18302-, 2014

PubMed 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(ϵ)-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.

PubMed: 24798337
DOI: 10.1074/JBC.M114.555052

Experimental method

X-RAY DIFFRACTION (1.8 Å)