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==Crystal structure of the fourth bromodomain of human poly-bromodomain containing protein 1 (PB1)==
==Crystal structure of the fourth bromodomain of human poly-bromodomain containing protein 1 (PB1)==
<StructureSection load='3tlp' size='340' side='right' caption='[[3tlp]], [[Resolution|resolution]] 2.13&Aring;' scene=''>
<StructureSection load='3tlp' size='340' side='right'caption='[[3tlp]], [[Resolution|resolution]] 2.13&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3tlp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TLP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TLP FirstGlance]. <br>
<table><tr><td colspan='2'>[[3tlp]] 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=3TLP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TLP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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]] 2.13&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAF180, PB1, PBRM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=3tlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tlp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tlp RCSB], [http://www.ebi.ac.uk/pdbsum/3tlp PDBsum]</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=3tlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tlp OCA], [https://pdbe.org/3tlp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tlp RCSB], [https://www.ebi.ac.uk/pdbsum/3tlp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tlp ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== 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>
[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 ==
== 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> 
[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>  
<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>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Allerston, C K]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H]]
[[Category: Allerston CK]]
[[Category: Bountra, C]]
[[Category: Arrowsmith CH]]
[[Category: Delft, F von]]
[[Category: Bountra C]]
[[Category: Edwards, A M]]
[[Category: Edwards AM]]
[[Category: Felletar, I]]
[[Category: Felletar I]]
[[Category: Filippakopoulos, P]]
[[Category: Filippakopoulos P]]
[[Category: Keates, T]]
[[Category: Keates T]]
[[Category: Knapp, S]]
[[Category: Knapp S]]
[[Category: Krojer, T]]
[[Category: Krojer T]]
[[Category: Latwiel, S]]
[[Category: Latwiel S]]
[[Category: Muniz, J]]
[[Category: Muniz J]]
[[Category: Picaud, S]]
[[Category: Picaud S]]
[[Category: Structural genomic]]
[[Category: Weigelt J]]
[[Category: Weigelt, J]]
[[Category: Von Delft F]]
[[Category: Baf180]]
[[Category: Brg1-associated factor 180]]
[[Category: Bromodomain]]
[[Category: Pb1]]
[[Category: Pbrm1]]
[[Category: Polybromo 1 isoform 1]]
[[Category: Polybromo-1d]]
[[Category: Sgc]]
[[Category: Transcription]]

Latest revision as of 16:33, 14 March 2024

Crystal structure of the fourth bromodomain of human poly-bromodomain containing protein 1 (PB1)Crystal structure of the fourth bromodomain of human poly-bromodomain containing protein 1 (PB1)

Structural highlights

3tlp is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.13Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PB1_HUMAN Defects in PBRM1 are a cause of renal cell carcinoma (RCC) [MIM: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.[1]

Function

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.[2]

References

  1. ↑ Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011 Jan 27;469(7331):539-42. doi: 10.1038/nature09639. Epub 2011 Jan 19. PMID:21248752 doi:10.1038/nature09639
  2. ↑ Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011 Jan 27;469(7331):539-42. doi: 10.1038/nature09639. Epub 2011 Jan 19. PMID:21248752 doi:10.1038/nature09639

3tlp, resolution 2.13Å

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