3mb4
From Proteopedia
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- | [[Image:3mb4.png|left|200px]] | ||
- | < | + | ==Crystal Structure of the fifth Bromodomain of Human Poly-bromodomain containing protein 1 (PB1) with NMP== |
- | + | <StructureSection load='3mb4' size='340' side='right'caption='[[3mb4]], [[Resolution|resolution]] 1.66Å' scene=''> | |
- | + | == Structural highlights == | |
- | or the | + | <table><tr><td colspan='2'>[[3mb4]] is a 2 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=3MB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MB4 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]] 1.66Å</td></tr> | |
- | - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MB3:1-METHYLPYRROLIDIN-2-ONE'>MB3</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=3mb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mb4 OCA], [https://pdbe.org/3mb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mb4 RCSB], [https://www.ebi.ac.uk/pdbsum/3mb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mb4 ProSAT]</span></td></tr> | |
+ | </table> | ||
+ | == Disease == | ||
+ | [https://www.uniprot.org/uniprot/PB1_HUMAN PB1_HUMAN] Defects in PBRM1 are a cause of renal cell carcinoma (RCC) [MIM:[https://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 == | ||
+ | [https://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> | ||
+ | == Evolutionary Conservation == | ||
+ | [[Image:Consurf_key_small.gif|200px|right]] | ||
+ | Check<jmol> | ||
+ | <jmolCheckbox> | ||
+ | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mb/3mb4_consurf.spt"</scriptWhenChecked> | ||
+ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
+ | <text>to colour the structure by Evolutionary Conservation</text> | ||
+ | </jmolCheckbox> | ||
+ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3mb4 ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family. | ||
- | + | Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331<ref>PMID:22464331</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | + | <div class="pdbe-citations 3mb4" style="background-color:#fffaf0;"></div> | |
- | + | == References == | |
- | + | <references/> | |
- | + | __TOC__ | |
- | + | </StructureSection> | |
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
- | [[Category: | + | [[Category: Large Structures]] |
- | [[Category: | + | [[Category: Arrowsmith CH]] |
- | [[Category: | + | [[Category: Bountra C]] |
- | [[Category: Edwards | + | [[Category: Edwards AM]] |
- | [[Category: Filippakopoulos | + | [[Category: Filippakopoulos P]] |
- | [[Category: Keates | + | [[Category: Keates T]] |
- | [[Category: Knapp | + | [[Category: Knapp S]] |
- | [[Category: Picaud | + | [[Category: Picaud S]] |
- | + | [[Category: Ugochukwu E]] | |
- | [[Category: Ugochukwu | + | [[Category: Weigelt J]] |
- | [[Category: Weigelt | + | [[Category: Von Delft F]] |
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Current revision
Crystal Structure of the fifth Bromodomain of Human Poly-bromodomain containing protein 1 (PB1) with NMP
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