View source for 3hmf


==Crystal Structure of the second Bromodomain of Human Poly-bromodomain containing protein 1 (PB1)==
<StructureSection load='3hmf' size='340' side='right' caption='[[3hmf]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3hmf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HMF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HMF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hme|3hme]], [[3hmh|3hmh]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PB1, PBRM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3hmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmf OCA], [http://pdbe.org/3hmf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hmf RCSB], [http://www.ebi.ac.uk/pdbsum/3hmf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmf ProSAT]</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>  
== 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/hm/3hmf_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=3hmf 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3hmf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Delft, F von]]
[[Category: Edwards, A]]
[[Category: Filippakopoulos, P]]
[[Category: Keates, T]]
[[Category: Knapp, S]]
[[Category: Muniz, J]]
[[Category: Picaud, S]]
[[Category: Structural genomic]]
[[Category: Weigelt, J]]
[[Category: Baf180]]
[[Category: Brg1-associated factor 180]]
[[Category: Bromodomain]]
[[Category: Chromatin regulator]]
[[Category: Dna-binding]]
[[Category: Nucleus]]
[[Category: Pb1]]
[[Category: Pbrm1]]
[[Category: Phosphoprotein]]
[[Category: Polybromo 1 isoform 1]]
[[Category: Polybromo-1d]]
[[Category: Sgc]]
[[Category: Transcription]]
[[Category: Transcription regulation]]