5v67 | pdb_00005v67

CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX WITH Volasertib

spinqualitylabelsall models 5v67, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5v67 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.78Å Ligands: DMS, EDO, IBI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease BRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein. Function BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMed BRD4 and other members of the bromodomain and extraterminal (BET) family of proteins are promising epigenetic targets for the development of novel therapeutics. Among the reported BRD4 inhibitors are dihydropteridinones and benzopyrimidodiazepinones originally designed to target the kinases PLK1, ERK5, and LRRK2. While these kinase inhibitors were identified as BRD4 inhibitors, little is known about their binding potential and structural details of interaction with the other BET bromodomains. We comprehensively characterized a series of known and newly identified dual BRD4-kinase inhibitors against all eight individual BET bromodomains. A detailed analysis of 23 novel cocrystal structures of BET-kinase inhibitor complexes in combination with direct binding assays and cell signaling studies revealed significant differences in molecular shape complementarity and inhibitory potential. Collectively, the data offer new insights into the action of kinase inhibitors across BET bromodomains, which may aid the development of drugs to inhibit certain BET proteins and kinases differentially. Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.,Karim RM, Bikowitz MJ, Chan A, Zhu JY, Grassie D, Becker A, Berndt N, Gunawan S, Lawrence NJ, Schonbrunn E J Med Chem. 2021 Nov 11;64(21):15772-15786. doi: 10.1021/acs.jmedchem.1c01096., Epub 2021 Oct 28. PMID:34710325 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bromodomain-containing protein 3D structures

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