5fh7

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the fifth bromodomain of human PB1 in complex with compound 18

Structural highlights

5fh7 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 1.47Å
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

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^[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
↑ Sutherell CL, Tallant C, Monteiro OP, Yapp C, Fuchs JE, Fedorov O, Siejka P, Muller S, Knapp S, Brenton JD, Brennan PE, Ley SV. Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex. J Med Chem. 2016 May 26;59(10):5095-101. doi: 10.1021/acs.jmedchem.5b01997. Epub , 2016 May 11. PMID:27119626 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01997

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5fh7"

@@ Line 3: / Line 3: @@
 <StructureSection load='5fh7' size='340' side='right'caption='[[5fh7]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5fh7]] is a 2 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=5FH7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FH7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5fh7]] 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=5FH7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FH7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.47&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PBRM1, BAF180, PB1 ([http://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=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://proteopedia.org/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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fh7 ProSAT]</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=5fh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fh7 OCA], [https://pdbe.org/5fh7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fh7 RCSB], [https://www.ebi.ac.uk/pdbsum/5fh7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fh7 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>
+[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 ==
-[[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 ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Brennan, P E]]
+[[Category: Brennan PE]]
-[[Category: Delft, F von]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M]]
+[[Category: Fedorov O]]
-[[Category: Fedorov, O]]
+[[Category: Knapp S]]
-[[Category: Knapp, S]]
+[[Category: Krojer T]]
-[[Category: Krojer, T]]
+[[Category: Ley SV]]
-[[Category: Ley, S V]]
+[[Category: Picaud S]]
-[[Category: Picaud, S]]
+[[Category: Siejka P]]
-[[Category: Siejka, P]]
+[[Category: Sorrell FJ]]
-[[Category: Sorrell, F J]]
+[[Category: Sutherell CL]]
-[[Category: Sutherell, C L]]
+[[Category: Tallant C]]
-[[Category: Tallant, C]]
+[[Category: Von Delft F]]
-[[Category: Brg1-associated factor 180]]
-[[Category: Chromatin remodeling]]
-[[Category: Pbrm1]]
-[[Category: Transcription]]

5fh7

From Proteopedia

Current revision

Crystal structure of the fifth bromodomain of human PB1 in complex with compound 18

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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