5FH6

Crystal structure of the fifth bromodomain of human PB1 in complex with compound 10

Summary for 5FH6

• Entry DOI: 10.2210/pdb5fh6/pdb
• Descriptor: Protein polybromo-1, (3~{R})-3-(piperidin-1-ylmethyl)-2,3-dihydro-1~{H}-pyrrolo[1,2-a]quinazolin-5-one (3 entities in total)
• Functional Keywords: pbrm1, brg1-associated factor 180, transcription, chromatin remodeling
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: Q86U86
• Total number of polymer chains: 4
• Total formula weight: 59725.47

Authors

Tallant, C.,Sutherell, C.L.,Siejka, P.,Krojer, T.,Picaud, S.,Fonseca, M.,Fedorov, O.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Brennan, P.E.,Ley, S.V.,Knapp, S. (deposition date: 2015-12-21, release date: 2016-06-01, Last modification date: 2024-01-10)

Primary citation

Sutherell, C.L.,Tallant, C.,Monteiro, O.P.,Yapp, C.,Fuchs, J.E.,Fedorov, O.,Siejka, P.,Muller, S.,Knapp, S.,Brenton, J.D.,Brennan, P.E.,Ley, S.V.
Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex.
J.Med.Chem., 59:5095-5101, 2016

PubMed Abstract: Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a KD of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4.

PubMed: 27119626
DOI: 10.1021/acs.jmedchem.5b01997

Experimental method

X-RAY DIFFRACTION (2.3 Å)