6u4a | pdb_00006u4a

BRD3-BD1 in complex with the cyclic peptide 3.1_3

spinqualitylabelsall models 6u4a, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6u4a is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.88Å Ligands: ACE, ALY, GOL, NH2, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease BRD3_HUMAN Note=A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUT which produces a BRD3-NUT fusion protein. Function BRD3_HUMAN Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors. Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity). Regulates transcription of the CCND1 gene. Publication Abstract from PubMed Cyclic peptide library screening technologies show immense promise for identifying drug leads and chemical probes for challenging targets. However, the structural and functional diversity encoded within such libraries is largely undefined. We have systematically profiled the affinity, selectivity, and structural features of library-derived cyclic peptides selected to recognize three closely related targets: the acetyllysine-binding bromodomain proteins BRD2, -3, and -4. We report affinities as low as 100 pM and specificities of up to 10(6)-fold. Crystal structures of 13 peptide-bromodomain complexes reveal remarkable diversity in both structure and binding mode, including both alpha-helical and beta-sheet structures as well as bivalent binding modes. The peptides can also exhibit a high degree of structural preorganization. Our data demonstrate the enormous potential within these libraries to provide diverse binding modes against a single target, which underpins their capacity to yield highly potent and selective ligands. Cyclic peptides can engage a single binding pocket through highly divergent modes.,Patel K, Walport LJ, Walshe JL, Solomon PD, Low JKK, Tran DH, Mouradian KS, Silva APG, Wilkinson-White L, Norman A, Franck C, Matthews JM, Guss JM, Payne RJ, Passioura T, Suga H, Mackay JP Proc Natl Acad Sci U S A. 2020 Oct 27;117(43):26728-26738. doi: , 10.1073/pnas.2003086117. Epub 2020 Oct 12. PMID:33046654 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bromodomain-containing protein 3D structures

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