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5MLJ

Bromodomain of Human GCN5 with 4-bromo-2-methyl-5-(((3R,5R)-1-methyl-5-phenylpiperidin-3-yl)amino)pyridazin-3(2H)-one

Summary for 5MLJ
Entry DOI10.2210/pdb5mlj/pdb
DescriptorHistone acetyltransferase KAT2A, 1,2-ETHANEDIOL, 4-bromo-2-methyl-5-[[(3~{R},5~{R})-1-methyl-5-phenyl-piperidin-3-yl]amino]pyridazin-3-one, ... (4 entities in total)
Functional Keywordsinhibitor, histone, epigenetic reader, bromodomain, gcn5, kat2a, antagonist, transcription
Biological sourceHomo sapiens (Human)
Cellular locationNucleus : Q92830
Total number of polymer chains2
Total formula weight27453.32
Authors
Chung, C.-W. (deposition date: 2016-12-06, release date: 2017-12-20, Last modification date: 2024-05-08)
Primary citationHumphreys, P.G.,Bamborough, P.,Chung, C.W.,Craggs, P.D.,Gordon, L.,Grandi, P.,Hayhow, T.G.,Hussain, J.,Jones, K.L.,Lindon, M.,Michon, A.M.,Renaux, J.F.,Suckling, C.J.,Tough, D.F.,Prinjha, R.K.
Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe.
J. Med. Chem., 60:695-709, 2017
Cited by
PubMed Abstract: p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and ≥18000-fold selectivity over the BET family, together with ≥70-fold selectivity over the wider bromodomain families.
PubMed: 28002667
DOI: 10.1021/acs.jmedchem.6b01566
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.8 Å)
Structure validation

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