5jsj - Revision history

OCA at 09:17, 20 March 2024

OCA — Wed, 20 Mar 2024 09:17:46 GMT

←Older revision		Revision as of 09:17, 20 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).		[https://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The discovery of inhibitors of methyl- and acetyl-binding domains has provided evidence for the 'druggability' of epigenetic effector molecules. The small-molecule probe UNC1215 prevents methyl-dependent protein-protein interactions by engaging the aromatic cage of MBT domains and, with lower affinity, Tudor domains. Using a library of tagged UNC1215 analogs, we screened a protein-domain microarray of human methyllysine effector molecules to rapidly detect compounds with new binding profiles with either increased or decreased specificity. Using this approach, we identified a compound (EML405) that acquired a novel interaction with the Tudor-domain-containing protein Spindlin1 (SPIN1). Structural studies facilitated the rational synthesis of SPIN1 inhibitors with increased selectivity (EML631-633), which engage SPIN1 in cells, block its ability to 'read' H3K4me3 marks and inhibit its transcriptional-coactivator activity. Protein microarrays can thus be used as a platform to 'target-hop' and identify small molecules that bind and compete with domain-motif interactions.
-
-	Developing Spindlin1 small-molecule inhibitors by using protein microarrays.,Bae N, Viviano M, Su X, Lv J, Cheng D, Sagum C, Castellano S, Bai X, Johnson C, Khalil MI, Shen J, Chen K, Li H, Sbardella G, Bedford MT Nat Chem Biol. 2017 Jul;13(7):750-756. doi: 10.1038/nchembio.2377. Epub 2017 May , 15. PMID:28504676<ref>PMID:28504676</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5jsj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Spindlin\|Spindlin]]		*[[Spindlin\|Spindlin]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 19:04, 20 September 2023

OCA — Wed, 20 Sep 2023 19:04:33 GMT

←Older revision		Revision as of 19:04, 20 September 2023
Line 1:		Line 1:

	==Crystal structure of Spindlin1 bound to compound EML631==		==Crystal structure of Spindlin1 bound to compound EML631==
-	<StructureSection load='5jsj' size='340' side='right' caption='[[5jsj]], [[Resolution\|resolution]] 2.35Å' scene=''>	+	<StructureSection load='5jsj' size='340' side='right'caption='[[5jsj]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5jsj]] 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=5JSJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5JSJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5jsj]] 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=5JSJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JSJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6PD:[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]-[4-[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]CARBONYL-3-[[4-(PYRROLIDIN-1-YLMETHOXY)PHENYL]AMINO]PHENYL]METHANONE'>6PD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.348Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5jsg\|5jsg]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6PD:[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]-[4-[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]CARBONYL-3-[[4-(PYRROLIDIN-1-YLMETHOXY)PHENYL]AMINO]PHENYL]METHANONE'>6PD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SPIN1, OCR, SPIN ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5jsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jsj OCA], [https://pdbe.org/5jsj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jsj RCSB], [https://www.ebi.ac.uk/pdbsum/5jsj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jsj ProSAT]</span></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=5jsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jsj OCA], [~~http~~://pdbe.org/5jsj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5jsj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5jsj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5jsj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN]] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).	+	[https://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5jsj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5jsj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Spindlin\|Spindlin]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Li, H~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Su, X~~]]	+	[[Category: Li H]]
-	[[Category: ~~Cell cycle]]~~	+	[[Category: Su X]]
-	~~[[Category: Tudor domain~~]]	+

OCA at 05:56, 16 November 2017

OCA — Thu, 16 Nov 2017 05:56:42 GMT

←Older revision		Revision as of 05:56, 16 November 2017
Line 3:		Line 3:
	<StructureSection load='5jsj' size='340' side='right' caption='[[5jsj]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='5jsj' size='340' side='right' caption='[[5jsj]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5jsj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JSJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5jsj]] 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=5JSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JSJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6PD:[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]-[4-[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]CARBONYL-3-[[4-(PYRROLIDIN-1-YLMETHOXY)PHENYL]AMINO]PHENYL]METHANONE'>6PD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6PD:[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]-[4-[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]CARBONYL-3-[[4-(PYRROLIDIN-1-YLMETHOXY)PHENYL]AMINO]PHENYL]METHANONE'>6PD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5jsg\|5jsg]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5jsg\|5jsg]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SPIN1, OCR, SPIN ([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=5jsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jsj OCA], [http://pdbe.org/5jsj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jsj RCSB], [http://www.ebi.ac.uk/pdbsum/5jsj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jsj ProSAT]</span></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=5jsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jsj OCA], [http://pdbe.org/5jsj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jsj RCSB], [http://www.ebi.ac.uk/pdbsum/5jsj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jsj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN]] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).		[[http://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN]] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The discovery of inhibitors of methyl- and acetyl-binding domains has provided evidence for the 'druggability' of epigenetic effector molecules. The small-molecule probe UNC1215 prevents methyl-dependent protein-protein interactions by engaging the aromatic cage of MBT domains and, with lower affinity, Tudor domains. Using a library of tagged UNC1215 analogs, we screened a protein-domain microarray of human methyllysine effector molecules to rapidly detect compounds with new binding profiles with either increased or decreased specificity. Using this approach, we identified a compound (EML405) that acquired a novel interaction with the Tudor-domain-containing protein Spindlin1 (SPIN1). Structural studies facilitated the rational synthesis of SPIN1 inhibitors with increased selectivity (EML631-633), which engage SPIN1 in cells, block its ability to 'read' H3K4me3 marks and inhibit its transcriptional-coactivator activity. Protein microarrays can thus be used as a platform to 'target-hop' and identify small molecules that bind and compete with domain-motif interactions.
		+
		+	Developing Spindlin1 small-molecule inhibitors by using protein microarrays.,Bae N, Viviano M, Su X, Lv J, Cheng D, Sagum C, Castellano S, Bai X, Johnson C, Khalil MI, Shen J, Chen K, Li H, Sbardella G, Bedford MT Nat Chem Biol. 2017 Jul;13(7):750-756. doi: 10.1038/nchembio.2377. Epub 2017 May , 15. PMID:28504676<ref>PMID:28504676</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5jsj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Su, X]]		[[Category: Su, X]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Tudor domain]]		[[Category: Tudor domain]]

OCA at 13:43, 24 May 2017

OCA — Wed, 24 May 2017 13:43:37 GMT

←Older revision		Revision as of 13:43, 24 May 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5jsj is ~~ON HOLD~~	+	==Crystal structure of Spindlin1 bound to compound EML631==
-		+	<StructureSection load='5jsj' size='340' side='right' caption='[[5jsj]], [[Resolution\|resolution]] 2.35Å' scene=''>
-	~~Authors~~: Su, X., Li, H.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5jsj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JSJ FirstGlance]. <br>
-	~~Description: Crystal structure of Spindlin1 bound to compound EML631~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6PD:[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]-[4-[4-(2-PYRROLIDIN-1-YLETHYL)PIPERIDIN-1-YL]CARBONYL-3-[[4-(PYRROLIDIN-1-YLMETHOXY)PHENYL]AMINO]PHENYL]METHANONE'>6PD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5jsg\|5jsg]]</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=5jsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jsj OCA], [http://pdbe.org/5jsj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jsj RCSB], [http://www.ebi.ac.uk/pdbsum/5jsj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jsj ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN]] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).
		+	__TOC__
		+	</StructureSection>
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Su, X]]		[[Category: Su, X]]
		+	[[Category: Cell cycle]]
		+	[[Category: Tudor domain]]

OCA at 07:08, 10 May 2017

OCA — Wed, 10 May 2017 07:08:48 GMT

←Older revision		Revision as of 07:08, 10 May 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5jsj is ON HOLD ~~until Paper Publication~~	+	The entry 5jsj is ON HOLD

-	Authors: Li, H., Su, X.	+	Authors: Su, X., Li, H.

	Description: Crystal structure of Spindlin1 bound to compound EML631		Description: Crystal structure of Spindlin1 bound to compound EML631

OCA at 10:00, 9 March 2017

OCA — Thu, 09 Mar 2017 10:00:59 GMT

←Older revision		Revision as of 10:00, 9 March 2017
Line 7:		Line 7:
	Description: Crystal structure of Spindlin1 bound to compound EML631		Description: Crystal structure of Spindlin1 bound to compound EML631
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Su, X]]
	[[Category: Li, H]]		[[Category: Li, H]]
		+	[[Category: Su, X]]

OCA at 12:07, 4 January 2017

OCA — Wed, 04 Jan 2017 12:07:53 GMT

←Older revision		Revision as of 12:07, 4 January 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5jsj is ON HOLD	+	The entry 5jsj is ON HOLD until Paper Publication

	Authors: Li, H., Su, X.		Authors: Li, H., Su, X.

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

OCA — Wed, 01 Jun 2016 13:46:43 GMT

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

←Older revision

Revision as of 13:46, 1 June 2016

OCA: New page: '''Unreleased structure''' The entry 5jsj is ON HOLD Authors: Li, H., Su, X. Description: Crystal structure of Spindlin1 bound to compound EML631 Category: Unreleased Structures [[...

OCA — Wed, 01 Jun 2016 13:46:42 GMT

New page: '''Unreleased structure''' The entry 5jsj is ON HOLD Authors: Li, H., Su, X. Description: Crystal structure of Spindlin1 bound to compound EML631 Category: Unreleased Structures [[...

New page

'''Unreleased structure'''

The entry 5jsj is ON HOLD

Authors: Li, H., Su, X.

Description: Crystal structure of Spindlin1 bound to compound EML631
[[Category: Unreleased Structures]]
[[Category: Su, X]]
[[Category: Li, H]]