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6zn6

From Proteopedia

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Protein polybromo-1 (PB1 BD2) Bound To MW278

Structural highlights

6zn6 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 2.02Å
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]

Publication Abstract from PubMed

Accessibility of the human genome is modulated by the ATP-driven SWI/SNF chromatin remodeling multiprotein complexes BAF (BRG1/BRM-associated factor) and PBAF (polybromo-associated BAF factor), which involves reading of acetylated histone tails by the bromodomain-containing proteins SMARCA2 (BRM), SMARCA4 (BRG1), and polybromo-1. Dysregulation of chromatin remodeling leads to aberrant cell proliferation and differentiation. Here, we have characterized a set of potent and cell-active bromodomain inhibitors with pan-selectivity for canonical family VIII bromodomains. Targeted SWI/SNF bromodomain inhibition blocked the expression of key genes during adipogenesis, including the transcription factors PPARgamma and C/EBPalpha, and impaired the differentiation of 3T3-L1 murine fibroblasts into adipocytes. Our data highlight the role of SWI/SNF bromodomains in adipogenesis and provide a framework for the development of SWI/SNF bromodomain inhibitors for indirect targeting of key transcription factors regulating cell differentiation.

Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis.,Wanior M, Preuss F, Ni X, Kramer A, Mathea S, Gobel T, Heidenreich D, Simonyi S, Kahnt AS, Joerger AC, Knapp S J Med Chem. 2020 Dec 10;63(23):14680-14699. doi: 10.1021/acs.jmedchem.0c01242., Epub 2020 Nov 20. PMID:33216538^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ Wanior M, Preuss F, Ni X, Kramer A, Mathea S, Gobel T, Heidenreich D, Simonyi S, Kahnt AS, Joerger AC, Knapp S. Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis. J Med Chem. 2020 Dec 10;63(23):14680-14699. doi: 10.1021/acs.jmedchem.0c01242., Epub 2020 Nov 20. PMID:33216538 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c01242

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6zn6"

@@ Line 3: / Line 3: @@
 <StructureSection load='6zn6' size='340' side='right'caption='[[6zn6]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6zn6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZN6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6zn6]] 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=6ZN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZN6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QMT:2-[6-azanyl-5-[(3~{R})-3-phenoxypiperidin-1-yl]pyridazin-3-yl]phenol'>QMT</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]] 2.02&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PBRM1, BAF180, PB1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QMT:2-[6-azanyl-5-[(3~{R})-3-phenoxypiperidin-1-yl]pyridazin-3-yl]phenol'>QMT</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=6zn6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zn6 OCA], [https://pdbe.org/6zn6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zn6 RCSB], [https://www.ebi.ac.uk/pdbsum/6zn6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zn6 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>
+[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>
+[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 ==
@@ Line 23: / Line 23: @@
 ==See Also==
-*[[Ribosome biogenesis protein|Ribosome biogenesis protein]]
+*[[Ribosome biogenesis protein 3D structures|Ribosome biogenesis protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chatterjee, D]]
+[[Category: Chatterjee D]]
-[[Category: Joerger, A C]]
+[[Category: Joerger AC]]
-[[Category: Knapp, S]]
+[[Category: Knapp S]]
-[[Category: Mathea, S]]
+[[Category: Mathea S]]
-[[Category: Preuss, F]]
+[[Category: Preuss F]]
-[[Category: Wanior, M]]
+[[Category: Wanior M]]
-[[Category: Bromodomain inhibitor epigenetic]]
-[[Category: Protein binding]]

6zn6

From Proteopedia

Current revision

Protein polybromo-1 (PB1 BD2) Bound To MW278

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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