5JI8
Crystal structure of the BRD9 bromodomain and hit 1
Summary for 5JI8
| Entry DOI | 10.2210/pdb5ji8/pdb |
| Descriptor | Bromodomain-containing protein 9, 2-amino-1,3-benzothiazole-6-carboxamide (3 entities in total) |
| Functional Keywords | brd9, bromodomain, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 13250.41 |
| Authors | |
| Primary citation | Wang, N.,Li, F.,Bao, H.,Li, J.,Wu, J.,Ruan, K. NMR Fragment Screening Hit Induces Plasticity of BRD7/9 Bromodomains Chembiochem, 17:1456-1463, 2016 Cited by PubMed Abstract: The complex biology associated with inhibition of bromodomain and extra-terminal (BET) domains by chemical probes has attracted increasing attention, and there is a need to identify non-BET bromodomain (BD) inhibitors. Several potent inhibitors of the BRD9 BD have recently been discovered, with anticancer and anti-inflammation activity. However, its paralogue, BRD7 BD, remains unexploited. Here, we identified new chemotypes targeting BRD7 BD by using NMR fragment-based screening. BRD7/9 BDs exhibit similar patterns of chemical-shift perturbation upon the titration of hit compound 1. The crystal structure revealed that 1 repels the Y222 group of BRD9 BD in a similar way to that for butyryllysine, but not acetyllysine and known inhibitors. Hit 1 induced less rearrangement of residue F161 of BRD9 BD than acetyllysine, butyryllysine, and crotonyllysine. Our study provides structural insight into a new generation of butyryllysine mimics for probing the function of BRD7/9 BD. PubMed: 27194508DOI: 10.1002/cbic.201600184 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.42 Å) |
Structure validation
Download full validation report
