4a9e | pdb_00004a9e

N-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 3-methyl-1,2,3,4- tetrahydroquinazolin-2-one

spinqualitylabelsall models 4a9e, resolution 1.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4a9e is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3PF, EDO, SO4 Related: 2yek, 1x0j, 2ydw, 4a9k, 4a9m, 4a9h, 4a9o, 4a9f, 4a9l, 4a9n, 4a9j, 4a9p, 4a9i Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed Bromodomain-containing proteins are key epigenetic regulators of gene transcription and readers of the histone code. However, the therapeutic benefits of modulating this target class are largely unexplored due to the lack of suitable chemical probes. This article describes the generation of lead molecules for the BET bromodomains through screening a fragment set chosen using structural insights and computational approaches. Analysis of 40 BRD2/fragment X-ray complexes highlights both shared and disparate interaction features, which that may be exploited for affinity and selectivity. Six representative crystal structures are then exemplified in detail. Two of the fragments are completely new bromodomain chemotypes, and three have never before been crystallized in a bromodomain, so our results significantly extend the limited public knowledge-base of crystallographic small molecule/bromodomain interactions. Certain fragments (including paracetamol) bind in a consistent mode to different bromodomains such as CREBBP, suggesting their potential to act as generic bromodomain templates. An important implication is that the bromodomains are not only a phylogenetic family, but also a system in which chemical and structural knowledge of one bromodomain gives insights transferrable to others. Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery.,Chung CW, Dean TW, Woolven JM, Bamborough P J Med Chem. 2011 Dec 5. PMID:22136404 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bromodomain-containing protein 3D structures

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