7JT4

Crystal Structure of BPTF bromodomain labelled with 5-fluoro-tryptophan

Summary for 7JT4

• Entry DOI: 10.2210/pdb7jt4/pdb
• Descriptor: Nucleosome-remodeling factor subunit BPTF (2 entities in total)
• Functional Keywords: gene regulation, bptf
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15426.41

Authors

Johnson, J.A.,Shi, K.,Aihara, H.,Pomerantz, W.C.K. (deposition date: 2020-08-17, release date: 2021-07-28, Last modification date: 2023-10-18)

Primary citation

Kirberger, S.E.,Ycas, P.D.,Johnson, J.A.,Chen, C.,Ciccone, M.F.,Woo, R.W.L.,Urick, A.K.,Zahid, H.,Shi, K.,Aihara, H.,McAllister, S.D.,Kashani-Sabet, M.,Shi, J.,Dickson, A.,Dos Santos, C.O.,Pomerantz, W.C.K.
Selectivity, ligand deconstruction, and cellular activity analysis of a BPTF bromodomain inhibitor
Org.Biomol.Chem., 17:2020-2027, 2019

PubMed Abstract: Bromodomain and PHD finger containing protein transcription factor (BPTF) is an epigenetic protein involved in chromatin remodelling and is a potential anticancer target. The BPTF bromodomain has one reported small molecule inhibitor (AU1, rac-1). Here, advances made on the structure-activity relationship of a BPTF bromodomain ligand are reported using a combination of experimental and molecular dynamics simulations leading to the active enatiomer (S)-1. Additionally, a ligand deconstruction analysis was conducted to characterize important pharmacophores for engaging the BPTF bromodomain. These studies have been enabled by a protein-based fluorine NMR approach, highlighting the versatility of the method for selectivity, ligand deconstruction, and ligand binding. To enable future analysis of biological activity, cell growth analyses in a panel of cancer cell lines were carried out using CRISPR-Cas9 and (S)-1 to identify cell-based model systems that are sensitive to BPTF inhibition.

PubMed: 30706071
DOI: 10.1039/c8ob02599a

Experimental method

X-RAY DIFFRACTION (2.06 Å)