6u72: Difference between revisions
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==BRD4-BD1 in complex with the cyclic peptide 3.1_2_AcK5toA== | |||
<StructureSection load='6u72' size='340' side='right'caption='[[6u72]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6u72]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U72 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6u72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u72 OCA], [https://pdbe.org/6u72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u72 RCSB], [https://www.ebi.ac.uk/pdbsum/6u72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u72 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/BRD4_HUMAN 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.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:33046654</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6u72" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Mackay | ==See Also== | ||
[[Category: Mouradian | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | ||
[[Category: Patel | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Mackay JP]] | |||
[[Category: Mouradian KS]] | |||
[[Category: Patel K]] | |||
[[Category: Walport LJ]] | |||
[[Category: Walshe JL]] | |||
Latest revision as of 10:45, 11 October 2023
BRD4-BD1 in complex with the cyclic peptide 3.1_2_AcK5toABRD4-BD1 in complex with the cyclic peptide 3.1_2_AcK5toA
Structural highlights
DiseaseBRD4_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.[1] [2] FunctionBRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMedCyclic 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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