5K4L

Crystal structure of KDM5A in complex with a naphthyridone inhibitor

Summary for 5K4L

• Entry DOI: 10.2210/pdb5k4l/pdb
• Descriptor: Lysine-specific demethylase 5A, Unknown Peptide, NICKEL (II) ION, ... (6 entities in total)
• Functional Keywords: epigenetics, demethylase, jumonji, inhibitor, cancer, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus, nucleolus : P29375
• Total number of polymer chains: 4
• Total formula weight: 183991.47

Authors

Kiefer, J.R.,Vinogradova, M.V. (deposition date: 2016-05-20, release date: 2016-08-10, Last modification date: 2024-10-23)

Primary citation

Labadie, S.S.,Dragovich, P.S.,Cummings, R.T.,Deshmukh, G.,Gustafson, A.,Han, N.,Harmange, J.C.,Kiefer, J.R.,Li, Y.,Liang, J.,Liederer, B.M.,Liu, Y.,Manieri, W.,Mao, W.,Murray, L.,Ortwine, D.F.,Trojer, P.,VanderPorten, E.,Vinogradova, M.,Wen, L.
Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.
Bioorg.Med.Chem.Lett., 26:4492-4496, 2016

PubMed Abstract: 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).

PubMed: 27499454
DOI: 10.1016/j.bmcl.2016.07.070

Experimental method

X-RAY DIFFRACTION (3.179 Å)