Structural highlights
Function
BRD2_HUMAN May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.[1]
Publication Abstract from PubMed
The BET (bromodomain and extra-terminal) family of proteins recognize the acetylated histone code on chromatin and play important roles in transcriptional co-regulation. BRD2 and BRD4, which belong to the BET family, are promising drug targets for the management of chronic diseases. The discovery of new scaffold molecules, a pyrano-1,3-oxazine derivative (NSC 328111; NS5) and phenanthridinone-based derivatives (L10 and its core moiety L10a), as inhibitors of BRD2 bromodomains BD1 and BD2, respectively, has recently been reported. The compound NS5 has a significant inhibitory effect on BRD2 in glioblastoma. Here, the crystal structure of BRD2 BD2 in complex with NS5, refined to 2.0 A resolution, is reported. Moreover, as the previously reported crystal structures of the BD1-NS5 complex and the BD2-L10a complex possess moderate electron density corresponding to the respective ligands, the crystal structures of these complexes were re-evaluated using new X-ray data. Together with biochemical studies using wild-type BRD2 BD1 and BD2 and various mutants, it is confirmed that the pyrano-1,3-oxazine and phenanthridinone derivatives are indeed potent inhibitors of BRD2 bromodomains.
Structural investigation of a pyrano-1,3-oxazine derivative and the phenanthridinone core moiety against BRD2 bromodomains.,Arole AH, Deshmukh P, Sridhar A, Padmanabhan B Acta Crystallogr F Struct Biol Commun. 2022 Mar 1;78(Pt 3):119-127. doi:, 10.1107/S2053230X22001066. Epub 2022 Feb 23. PMID:35234137[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ LeRoy G, Rickards B, Flint SJ. The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol Cell. 2008 Apr 11;30(1):51-60. doi: 10.1016/j.molcel.2008.01.018. PMID:18406326 doi:10.1016/j.molcel.2008.01.018
- ↑ Arole AH, Deshmukh P, Sridhar A, Padmanabhan B. Structural investigation of a pyrano-1,3-oxazine derivative and the phenanthridinone core moiety against BRD2 bromodomains. Acta Crystallogr F Struct Biol Commun. 2022 Mar 1;78(Pt 3):119-127. doi:, 10.1107/S2053230X22001066. Epub 2022 Feb 23. PMID:35234137 doi:http://dx.doi.org/10.1107/S2053230X22001066
