5k4l

Crystal structure of KDM5A in complex with a naphthyridone inhibitor

spinqualitylabelsall models 5k4l, resolution 3.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5k4l is a 4 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 3.179Å Ligands: 6QN, NI, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KDM5A_HUMAN Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May stimulate transcription mediated by nuclear receptors. May be involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity).[UniProtKB:Q3UXZ9] Publication Abstract from PubMed Features from a high throughput screening (HTS) hit and a previously reported scaffold were combined to generate 1,7-naphthyridones as novel KDM5 enzyme inhibitors with nanomolar potencies. These molecules exhibited high selectivity over the related KDM4C and KDM2B isoforms. An X-ray co-crystal structure of a representative molecule bound to KDM5A showed that these inhibitors are competitive with the co-substrate (2-oxoglutarate or 2-OG). Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.,Labadie SS, Dragovich PS, Cummings RT, Deshmukh G, Gustafson A, Han N, Harmange JC, Kiefer JR, Li Y, Liang J, Liederer BM, Liu Y, Manieri W, Mao W, Murray L, Ortwine DF, Trojer P, VanderPorten E, Vinogradova M, Wen L Bioorg Med Chem Lett. 2016 Sep 15;26(18):4492-6. doi: 10.1016/j.bmcl.2016.07.070., Epub 2016 Jul 29. PMID:27499454 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Jumonji domain-containing protein 3D structures Lysine-specific histone demethylase 3D structures

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