7uq3

JmjC domain-containing protein 5 (JMJD5) in complex with Mn and (S)-2-(1-hydroxy-2,5-dioxopyrrolidin-3-yl)acetic acid

spinqualitylabelsall models 7uq3, resolution 1.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7uq3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.49Å Ligands: GOL, MN, O2U Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KDM8_HUMAN Histone demethylase required for G2/M phase cell cycle progression. Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator. Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation. Publication Abstract from PubMed JmjC (Jumonji-C) domain-containing 5 (JMJD5) plays important roles in circadian regulation in plants and humans and is involved in embryonic development and cell proliferation. JMJD5 is a 2-oxoglutarate (2OG) and Fe(II) dependent oxygenase of the JmjC subfamily, which includes histone N(epsilon)-methyl lysine-demethylases (KDMs) and hydroxylases catalysing formation of stable alcohol products. JMJD5 is reported to have KDM activity, but has been shown to catalyse C-3 hydroxylation of arginine residues in sequences from human regulator of chromosome condensation domain-containing protein 1 (RCCD1) and ribosomal protein S6 (RPS6) in vitro. We report crystallographic analyses of human JMJD5 complexed with 2OG analogues, including the widely used hypoxia mimic pyridine-2,4-dicarboxylate, both D- and L-enantiomers of the oncometabolite 2-hydroxyglutarate, and a cyclic N-hydroxyimide. The results support the assignment of JMJD5 as a protein hydroxylase and reveal JMJD5 has an unusually compact 2OG binding pocket suitable for exploitation in development of selective inhibitors. They will be useful in the development of chemical probes to investigate the physiologically relevant roles of JMJD5 in circadian rhythm and development and explore its potential as a medicinal chemistry target. Structural analysis of the 2-oxoglutarate binding site of the circadian rhythm linked oxygenase JMJD5.,Islam MS, Markoulides M, Chowdhury R, Schofield CJ Sci Rep. 2022 Nov 30;12(1):20680. doi: 10.1038/s41598-022-24154-0. PMID:36450832 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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