5fh7
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the fifth bromodomain of human PB1 in complex with compound 18== | |
| + | <StructureSection load='5fh7' size='340' side='right' caption='[[5fh7]], [[Resolution|resolution]] 1.47Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5fh7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FH7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FH7 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5XL:6-CHLORANYL-3-[(DIMETHYLAMINO)METHYL]-4~{H}-PYRROLO[1,2-A]QUINAZOLIN-5-ONE'>5XL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fh7 OCA], [http://pdbe.org/5fh7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fh7 RCSB], [http://www.ebi.ac.uk/pdbsum/5fh7 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/PB1_HUMAN PB1_HUMAN]] Defects in PBRM1 are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. It is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:21248752</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PB1_HUMAN PB1_HUMAN]] Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Acts as a negative regulator of cell proliferation.<ref>PMID:21248752</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a KD of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4. | ||
| - | + | Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex.,Sutherell CL, Tallant C, Monteiro OP, Yapp C, Fuchs JE, Fedorov O, Siejka P, Muller S, Knapp S, Brenton JD, Brennan PE, Ley SV J Med Chem. 2016 May 26;59(10):5095-101. doi: 10.1021/acs.jmedchem.5b01997. Epub , 2016 May 11. PMID:27119626<ref>PMID:27119626</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5fh7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Arrowsmith, C H]] | ||
| + | [[Category: Bountra, C]] | ||
| + | [[Category: Brennan, P E]] | ||
| + | [[Category: Delft, F von]] | ||
| + | [[Category: Edwards, A M]] | ||
[[Category: Fedorov, O]] | [[Category: Fedorov, O]] | ||
| - | [[Category: Picaud, S]] | ||
| - | [[Category: Siejka, P]] | ||
[[Category: Knapp, S]] | [[Category: Knapp, S]] | ||
[[Category: Krojer, T]] | [[Category: Krojer, T]] | ||
| - | [[Category: | + | [[Category: Ley, S V]] |
| - | [[Category: | + | [[Category: Picaud, S]] |
| - | [[Category: | + | [[Category: Siejka, P]] |
| - | [[Category: | + | [[Category: Sorrell, F J]] |
| - | [[Category: Sutherell, C | + | [[Category: Sutherell, C L]] |
| - | + | ||
| - | + | ||
| - | + | ||
[[Category: Tallant, C]] | [[Category: Tallant, C]] | ||
| + | [[Category: Brg1-associated factor 180]] | ||
| + | [[Category: Chromatin remodeling]] | ||
| + | [[Category: Pbrm1]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 15:41, 1 June 2016
Crystal structure of the fifth bromodomain of human PB1 in complex with compound 18
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