5d3h
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5d3h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D3H FirstGlance]. <br> | <table><tr><td colspan='2'>[[5d3h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D3H FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=57G:N-[5-(DIETHYLSULFAMOYL)-2-HYDROXYPHENYL]-3-ETHYL-4-(HYDROXYACETYL)-5-METHYL-1H-PYRROLE-2-CARBOXAMIDE'>57G</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=57G:N-[5-(DIETHYLSULFAMOYL)-2-HYDROXYPHENYL]-3-ETHYL-4-(HYDROXYACETYL)-5-METHYL-1H-PYRROLE-2-CARBOXAMIDE'>57G</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=5d3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d3h OCA], [https://pdbe.org/5d3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d3h RCSB], [https://www.ebi.ac.uk/pdbsum/5d3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d3h ProSAT]</span></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=5d3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d3h OCA], [https://pdbe.org/5d3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d3h RCSB], [https://www.ebi.ac.uk/pdbsum/5d3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d3h ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | [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 == | ||
| - | Several human diseases, including cancer, show altered signaling pathways resulting from changes in the activity levels of epigenetic modulators. In the past few years, small-molecule inhibitors against specific modulators, including the bromodomain and extra-terminal (BET) bromodomain family of acetylation readers, have shown early promise in the treatment of the genetically defined midline carcinoma and hematopoietic malignancies. We have recently developed a novel potent inhibitor of BET proteins, 1 (XD14[ Angew. Chem., Int. Ed. 2013 , 52 , 14055 ]), which exerts a strong inhibitory potential on the proliferation of specific leukemia cell lines. In the study presented here, we designed analogues of 1 to study the potential of substitutions on the 4-acyl pyrrole backbone to occupy additional sites within the substrate recognition site of BRD4(1). The compounds were profiled using ITC, DSF, and X-ray crystallography. We could introduce several substitutions that address previously untargeted areas of the substrate recognition site. This work may substantially contribute to the development of therapeutics with increased target specificity against BRD4-related malignancies. | ||
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| - | 4-Acyl Pyrrole Derivatives Yield Novel Vectors for Designing Inhibitors of the Acetyl-Lysine Recognition Site of BRD4(1).,Hugle M, Lucas X, Weitzel G, Ostrovskyi D, Breit B, Gerhardt S, Einsle O, Gunther S, Wohlwend D J Med Chem. 2016 Jan 14. PMID:26731611<ref>PMID:26731611</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 5d3h" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
First bromodomain of BRD4 bound to inhibitor XD29
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