5hrw - Revision history

OCA at 10:52, 16 August 2023

OCA — Wed, 16 Aug 2023 10:52:09 GMT

←Older revision		Revision as of 10:52, 16 August 2023
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	<StructureSection load='5hrw' size='340' side='right'caption='[[5hrw]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='5hrw' size='340' side='right'caption='[[5hrw]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hrw]] 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=5HRW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5HRW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hrw]] 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=5HRW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HRW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=64E:1-PROPYLISOCHROMENO[3,4-C]PYRAZOL-5(3H)-ONE'>64E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.8Å</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=64E:1-PROPYLISOCHROMENO[3,4-C]PYRAZOL-5(3H)-ONE'>64E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5hrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hrw OCA], [~~http~~://pdbe.org/5hrw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5hrw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5hrw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5hrw 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=5hrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hrw OCA], [https://pdbe.org/5hrw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hrw RCSB], [https://www.ebi.ac.uk/pdbsum/5hrw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hrw 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arrowsmith~~, C H~~]]	+	[[Category: Arrowsmith CH]]
-	[[Category: Bountra, C]]	+	[[Category: Bountra C]]
-	~~[[Category: Delft, F von~~]]	+	[[Category: Edwards AM]]
-	[[Category: Edwards~~, A M~~]]	+	[[Category: Gaboriaud-Kolar N]]
-	[[Category: Gaboriaud-Kolar, N]]	+	[[Category: Knapp S]]
-	[[Category: Knapp, S]]	+	[[Category: Mikros E]]
-	[[Category: Mikros, E]]	+	[[Category: Myrianthopoulos V]]
-	[[Category: Myrianthopoulos, V]]	+	[[Category: Newman JA]]
-	[[Category: Newman~~, J A~~]]	+	[[Category: Picaud S]]
-	[[Category: Picaud, S]]	+	[[Category: Tallant C]]
-	[[Category: Tallant, C]]	+	[[Category: Von Delft F]]
-	[[Category: ~~Brg1-associated factor 180]]~~	+
-	~~[[Category: Chromatin remodeling]]~~	+
-	~~[[Category: Pbrm1]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 08:29, 27 May 2020

OCA — Wed, 27 May 2020 08:29:52 GMT

←Older revision		Revision as of 08:29, 27 May 2020
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	==Crystal structure of the fifth bromodomain of human PB1 in complex with 1-propylisochromeno[3,4-c]pyrazol-5(2H)-one) compound==		==Crystal structure of the fifth bromodomain of human PB1 in complex with 1-propylisochromeno[3,4-c]pyrazol-5(2H)-one) compound==
-	<StructureSection load='5hrw' size='340' side='right' caption='[[5hrw]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='5hrw' size='340' side='right'caption='[[5hrw]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hrw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HRW OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5HRW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hrw]] 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=5HRW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HRW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=64E:1-PROPYLISOCHROMENO[3,4-C]PYRAZOL-5(3H)-ONE'>64E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=64E:1-PROPYLISOCHROMENO[3,4-C]PYRAZOL-5(3H)-ONE'>64E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5hrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hrw OCA], [http://pdbe.org/5hrw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hrw RCSB], [http://www.ebi.ac.uk/pdbsum/5hrw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hrw ProSAT]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hrw OCA], [http://pdbe.org/5hrw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hrw RCSB], [http://www.ebi.ac.uk/pdbsum/5hrw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hrw ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]
	[[Category: Bountra, C]]		[[Category: Bountra, C]]

OCA at 17:40, 19 October 2016

OCA — Wed, 19 Oct 2016 17:40:57 GMT

←Older revision		Revision as of 17:40, 19 October 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5hrw is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the fifth bromodomain of human PB1 in complex with 1-propylisochromeno[3,4-c]pyrazol-5(2H)-one) compound==
		+	<StructureSection load='5hrw' size='340' side='right' caption='[[5hrw]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5hrw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HRW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HRW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=64E:1-PROPYLISOCHROMENO[3,4-C]PYRAZOL-5(3H)-ONE'>64E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5hrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hrw OCA], [http://pdbe.org/5hrw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hrw RCSB], [http://www.ebi.ac.uk/pdbsum/5hrw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hrw 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Bromodomains (BRDs) are epigenetic interaction domains currently recognized as emerging drug targets for development of anticancer or anti-inflammatory agents. In this study, development of a selective ligand of the fifth BRD of polybromo protein-1 (PB1(5)) related to switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes is presented. A compound collection was evaluated by consensus virtual screening and a hit was identified. The biophysical study of protein-ligand interactions was performed using X-ray crystallography and isothermal titration calorimetry. Collective data supported the hypothesis that affinity improvement could be achieved by enhancing interactions of the complex with the solvent. The derived SAR along with free energy calculations and a consensus hydration analysis using WaterMap and SZmap algorithms guided rational design of a set of novel analogues. The most potent analogue demonstrated high affinity of 3.3 muM and an excellent selectivity profile, thus comprising a promising lead for the development of chemical probes targeting PB1(5).

-	~~Authors: Tallant, C~~., Myrianthopoulos, V., Gaboriaud-Kolar, N., ~~Newman~~, ~~J.A., Picaud~~, S., ~~von Delft~~, ~~F., Arrowsmith~~, C~~.H.~~, ~~Edwards~~, A.M., ~~Bountra~~, C., ~~Mikros~~, E., ~~Knapp~~, S.	+	Discovery and Optimization of a Selective Ligand for the Switch/Sucrose Nonfermenting-Related Bromodomains of Polybromo Protein-1 by the Use of Virtual Screening and Hydration Analysis.,Myrianthopoulos V, Gaboriaud-Kolar N, Tallant C, Hall ML, Grigoriou S, Brownlee PM, Fedorov O, Rogers C, Heidenreich D, Wanior M, Drosos N, Mexia N, Savitsky P, Bagratuni T, Kastritis E, Terpos E, Filippakopoulos P, Muller S, Skaltsounis AL, Downs JA, Knapp S, Mikros E J Med Chem. 2016 Oct 13;59(19):8787-8803. Epub 2016 Sep 27. PMID:27617704<ref>PMID:27617704</ref>

-	~~Description: Crystal structure~~ of the ~~fifth bromodomain~~ of ~~human PB1 in complex with 1~~-~~propylisochromeno~~[3,~~4-c~~]~~pyrazol-5(2H)-one) compound~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Picaud~~, S]]	+	<div class="pdbe-citations 5hrw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Arrowsmith, C H]]
		+	[[Category: Bountra, C]]
		+	[[Category: Delft, F von]]
		+	[[Category: Edwards, A M]]
		+	[[Category: Gaboriaud-Kolar, N]]
	[[Category: Knapp, S]]		[[Category: Knapp, S]]
	[[Category: Mikros, E]]		[[Category: Mikros, E]]
-	[[Category: Gaboriaud-Kolar, N]]
-	[[Category: Bountra, C]]
	[[Category: Myrianthopoulos, V]]		[[Category: Myrianthopoulos, V]]
-	[[Category: ~~Arrowsmith, C.H]]~~	+	[[Category: Newman, J A]]
-	~~[[Category: Von Delft, F]]~~	+	[[Category: Picaud, S]]
-	~~[[Category: Edwards~~, A.M]]	+
-	[[Category: ~~Newman~~, ~~J.A~~]]	+
	[[Category: Tallant, C]]		[[Category: Tallant, C]]
		+	[[Category: Brg1-associated factor 180]]
		+	[[Category: Chromatin remodeling]]
		+	[[Category: Pbrm1]]
		+	[[Category: Transcription]]

OCA: Protected "5hrw" [edit=sysop:move=sysop]

OCA — Wed, 03 Feb 2016 14:14:23 GMT

Protected "5hrw" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:14, 3 February 2016

OCA: New page: '''Unreleased structure''' The entry 5hrw is ON HOLD until Paper Publication Authors: Tallant, C., Myrianthopoulos, V., Gaboriaud-Kolar, N., Newman, J.A., Picaud, S., von Delft, F., Arr...

OCA — Wed, 03 Feb 2016 14:14:21 GMT

New page: '''Unreleased structure''' The entry 5hrw is ON HOLD until Paper Publication Authors: Tallant, C., Myrianthopoulos, V., Gaboriaud-Kolar, N., Newman, J.A., Picaud, S., von Delft, F., Arr...

New page

'''Unreleased structure'''

The entry 5hrw is ON HOLD until Paper Publication

Authors: Tallant, C., Myrianthopoulos, V., Gaboriaud-Kolar, N., Newman, J.A., Picaud, S., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Mikros, E., Knapp, S.

Description: Crystal structure of the fifth bromodomain of human PB1 in complex with 1-propylisochromeno[3,4-c]pyrazol-5(2H)-one) compound
[[Category: Unreleased Structures]]
[[Category: Picaud, S]]
[[Category: Knapp, S]]
[[Category: Mikros, E]]
[[Category: Gaboriaud-Kolar, N]]
[[Category: Bountra, C]]
[[Category: Myrianthopoulos, V]]
[[Category: Arrowsmith, C.H]]
[[Category: Von Delft, F]]
[[Category: Edwards, A.M]]
[[Category: Newman, J.A]]
[[Category: Tallant, C]]