5exa - Revision history

OCA at 08:31, 12 July 2023

2023-07-12T08:31:21Z

←Older revision		Revision as of 08:31, 12 July 2023
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	==Small-molecule stabilization of the 14-3-3/Gab2 PPI interface==		==Small-molecule stabilization of the 14-3-3/Gab2 PPI interface==
-	<StructureSection load='5exa' size='340' side='right' caption='[[5exa]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='5exa' size='340' side='right'caption='[[5exa]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5exa]] is a 4 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=5EXA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5EXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5exa]] is a 4 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=5EXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EXA FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=5SO:FUSICOCCIN+A~~-~~THF+DERIVATIVE'>5SO</scene>~~, ~~<scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.95Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~TPO~~:~~PHOSPHOTHREONINE~~'>~~TPO~~</scene><~~/td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5SO:FUSICOCCIN+A-THF+DERIVATIVE'>5SO</scene>, <scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<~~tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b~~></td>~~<td class="sblockDat">[[3cu8\|3cu8]]~~, ~~[[4fj3\|4fj3]], [[4ihl\|4ihl]], [[4n7y\|4n7y]]~~<~~/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=5exa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exa OCA], [https://pdbe.org/5exa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5exa RCSB], [https://www.ebi.ac.uk/pdbsum/5exa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5exa ProSAT]</span></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">YWHAZ ([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=5exa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exa OCA], [~~http~~://pdbe.org/5exa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5exa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5exa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5exa ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> [[http://www.uniprot.org/uniprot/GAB2_HUMAN GAB2_HUMAN]] Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis.<ref>PMID:15750601</ref> <ref>PMID:19172738</ref>	+	[https://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 21:

	==See Also==		==See Also==
-	*[[14-3-3 protein\|14-3-3 protein]]	+	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Bier, D~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Ottmann, C~~]]	+	[[Category: Bier D]]
-	[[Category: ~~14-3-3]]~~	+	[[Category: Ottmann C]]
-	~~[[Category: Diphosphorylation]]~~	+
-	~~[[Category: Gab2]]~~	+
-	~~[[Category: Protein]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 08:40, 19 December 2018

2018-12-19T08:40:35Z

←Older revision		Revision as of 08:40, 19 December 2018
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	<StructureSection load='5exa' size='340' side='right' caption='[[5exa]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5exa' size='340' side='right' caption='[[5exa]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5exa]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5exa]] is a 4 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=5EXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EXA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5SO:FUSICOCCIN+A-THF+DERIVATIVE'>5SO</scene>, <scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5SO:FUSICOCCIN+A-THF+DERIVATIVE'>5SO</scene>, <scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cu8\|3cu8]], [[4fj3\|4fj3]], [[4ihl\|4ihl]], [[4n7y\|4n7y]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cu8\|3cu8]], [[4fj3\|4fj3]], [[4ihl\|4ihl]], [[4n7y\|4n7y]]</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=5exa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exa OCA], [http://pdbe.org/5exa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exa RCSB], [http://www.ebi.ac.uk/pdbsum/5exa PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([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=5exa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exa OCA], [http://pdbe.org/5exa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exa RCSB], [http://www.ebi.ac.uk/pdbsum/5exa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5exa ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5exa" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5exa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[14-3-3 protein\|14-3-3 protein]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Bier, D]]		[[Category: Bier, D]]
	[[Category: Ottmann, C]]		[[Category: Ottmann, C]]

OCA at 03:28, 11 May 2016

2016-05-11T03:28:54Z

←Older revision		Revision as of 03:28, 11 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5exa is ~~ON HOLD~~	+	==Small-molecule stabilization of the 14-3-3/Gab2 PPI interface==
		+	<StructureSection load='5exa' size='340' side='right' caption='[[5exa]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5exa]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EXA FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5SO:FUSICOCCIN+A-THF+DERIVATIVE'>5SO</scene>, <scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cu8\|3cu8]], [[4fj3\|4fj3]], [[4ihl\|4ihl]], [[4n7y\|4n7y]]</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=5exa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exa OCA], [http://pdbe.org/5exa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exa RCSB], [http://www.ebi.ac.uk/pdbsum/5exa PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> [[http://www.uniprot.org/uniprot/GAB2_HUMAN GAB2_HUMAN]] Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis.<ref>PMID:15750601</ref> <ref>PMID:19172738</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Small-molecule modulation of protein-protein interactions (PPIs) is one of the most promising new areas in drug discovery. In the vast majority of cases only inhibition or disruption of PPIs is realized, whereas the complementary strategy of targeted stabilization of PPIs is clearly under-represented. Here, we report the example of a semi-synthetic natural product derivative-ISIR-005-that stabilizes the cancer-relevant interaction of the adaptor protein 14-3-3 and Gab2. The crystal structure of ISIR-005 in complex with 14-3-3 and the binding motif of Gab2 comprising two phosphorylation sites (Gab2pS210pT391) showed how the stabilizing molecule binds to the rim-of-the-interface of the protein complex. Only in the direct vicinity of 14-3-3/Gab2pT391 site is a pre-formed pocket occupied by ISIR-005; binding of the Gab2pS210 motif to 14-3-3 does not create an interface pocket suitable for the molecule. Accordingly, ISIR-005 only stabilizes the binding of the Gab2pT391 but not the Gab2pS210 site. This study represents structural and biochemical proof of the druggability of the 14-3-3/Gab2 PPI interface with important implications for the development of PPI stabilizers.

-	~~Authors: Bier~~, D., ~~Ottmann~~, C.	+	Small-Molecule Stabilization of the 14-3-3/Gab2 Protein-Protein Interaction (PPI) Interface.,Bier D, Bartel M, Sies K, Halbach S, Higuchi Y, Haranosono Y, Brummer T, Kato N, Ottmann C ChemMedChem. 2016 Apr 19;11(8):911-8. doi: 10.1002/cmdc.201500484. Epub 2015 Dec , 8. PMID:26644359<ref>PMID:26644359</ref>

-	~~Description: Small-molecule stabilization~~ of the 14-3-3/~~Gab2 PPI interface~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category: Ottmann, C]]~~	+	<div class="pdbe-citations 5exa" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Bier, D]]		[[Category: Bier, D]]
		+	[[Category: Ottmann, C]]
		+	[[Category: 14-3-3]]
		+	[[Category: Diphosphorylation]]
		+	[[Category: Gab2]]
		+	[[Category: Protein]]
		+	[[Category: Signaling protein]]

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

2015-12-02T15:06:50Z

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

←Older revision

Revision as of 15:06, 2 December 2015

OCA: New page: '''Unreleased structure''' The entry 5exa is ON HOLD Authors: Bier, D., Ottmann, C. Description: Small-molecule stabilization of the 14-3-3/Gab2 PPI interface [[Category: Unreleased St...

2015-12-02T15:06:49Z

New page: '''Unreleased structure''' The entry 5exa is ON HOLD Authors: Bier, D., Ottmann, C. Description: Small-molecule stabilization of the 14-3-3/Gab2 PPI interface [[Category: Unreleased St...

New page

'''Unreleased structure'''

The entry 5exa is ON HOLD

Authors: Bier, D., Ottmann, C.

Description: Small-molecule stabilization of the 14-3-3/Gab2 PPI interface
[[Category: Unreleased Structures]]
[[Category: Ottmann, C]]
[[Category: Bier, D]]