6i8b - Revision history

OCA at 11:49, 24 January 2024

2024-01-24T11:49:08Z

←Older revision		Revision as of 11:49, 24 January 2024
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	==Crystal structure of Spindlin1 in complex with the inhibitor VinSpinIn==		==Crystal structure of Spindlin1 in complex with the inhibitor VinSpinIn==
-	<StructureSection load='6i8b' size='340' side='right' caption='[[6i8b]], [[Resolution\|resolution]] 1.76Å' scene=''>	+	<StructureSection load='6i8b' size='340' side='right'caption='[[6i8b]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6i8b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I8B OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6I8B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6i8b]] 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=6I8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I8B FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=H7T:2-[4-[2-[[2-[3-[2-azanyl-5-(cyclopropylmethoxy)-3,3-dimethyl-indol-6-yl]oxypropyl]-1,3-dihydroisoindol-5-yl]oxy]ethyl]-1,2,3-triazol-1-yl]-1-[4-(2-pyrrolidin-1-ylethyl)piperidin-1-yl]ethanone'>H7T</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.76Å</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=6i8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i8b OCA], [~~http~~://pdbe.org/6i8b PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6i8b RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6i8b PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6i8b ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=H7T:2-[4-[2-[[2-[3-[2-azanyl-5-(cyclopropylmethoxy)-3,3-dimethyl-indol-6-yl]oxypropyl]-1,3-dihydroisoindol-5-yl]oxy]ethyl]-1,2,3-triazol-1-yl]-1-[4-(2-pyrrolidin-1-ylethyl)piperidin-1-yl]ethanone'>H7T</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6i8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i8b OCA], [https://pdbe.org/6i8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i8b RCSB], [https://www.ebi.ac.uk/pdbsum/6i8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i8b 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;">
		+	== Publication Abstract from PubMed ==
		+	Modifications of histone tails, including lysine/arginine methylation, provide the basis of a "chromatin or histone code". Proteins that contain "reader" domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader domains and was identified as a putative oncogene and transcriptional coactivator. Here we report a SPIN1 chemical probe inhibitor with low nanomolar in vitro activity, exquisite selectivity on a panel of methyl reader and writer proteins, and with submicromolar cellular activity. X-ray crystallography showed that this Tudor domain chemical probe simultaneously engages Tudor domains 1 and 2 via a bidentate binding mode. Small molecule inhibition and siRNA knockdown of SPIN1, as well as chemoproteomic studies, identified genes which are transcriptionally regulated by SPIN1 in squamous cell carcinoma and suggest that SPIN1 may have a role in cancer related inflammation and/or cancer metastasis.
		+
		+	A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function.,Fagan V, Johansson C, Gileadi C, Monteiro O, Dunford JE, Nibhani R, Philpott M, Malzahn J, Wells G, Faram R, Cribbs AP, Halidi N, Li F, Chau I, Greschik H, Velupillai S, Allali-Hassani A, Bennett J, Christott T, Giroud C, Lewis AM, Huber KVM, Athanasou N, Bountra C, Jung M, Schule R, Vedadi M, Arrowsmith C, Xiong Y, Jin J, Fedorov O, Farnie G, Brennan PE, Oppermann U J Med Chem. 2019 Oct 24;62(20):9008-9025. doi: 10.1021/acs.jmedchem.9b00562. Epub , 2019 Oct 15. PMID:31550156<ref>PMID:31550156</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6i8b" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Spindlin\|Spindlin]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Arrowsmith, C H~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Bountra, C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Brennan, P E~~]]	+	[[Category: Arrowsmith CH]]
-	[[Category: ~~Edwards, A~~]]	+	[[Category: Bountra C]]
-	[[Category: ~~Fagan, V~~]]	+	[[Category: Brennan PE]]
-	[[Category: ~~Johansson, C~~]]	+	[[Category: Edwards A]]
-	[[Category: ~~Krojer, T~~]]	+	[[Category: Fagan V]]
-	[[Category: ~~Oppermann, U~~ C.T]]	+	[[Category: Johansson C]]
-	[[Category: ~~Sorrell, F J~~]]	+	[[Category: Krojer T]]
-	[[Category: ~~Cell cycle~~]]	+	[[Category: Oppermann UCT]]
-	[[Category: ~~Epigenetic]]~~	+	[[Category: Sorrell FJ]]
-	~~[[Category: Methyl-arginine]]~~	+
-	~~[[Category: Methyl-lysine]]~~	+
-	~~[[Category: Tudor domain~~]]	+

OCA at 06:48, 5 December 2018

2018-12-05T06:48:24Z

←Older revision		Revision as of 06:48, 5 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6i8b ~~is ON HOLD~~	+	==Crystal structure of Spindlin1 in complex with the inhibitor VinSpinIn==
-		+	<StructureSection load='6i8b' size='340' side='right' caption='[[6i8b]], [[Resolution\|resolution]] 1.76Å' scene=''>
-	~~Authors~~: ~~Johansson, C~~., ~~Fagan~~, V., ~~Brennan~~, ~~P.E.~~, ~~Sorrell~~, F.J.~~, Krojer, T~~., ~~Arrowsmith, C~~.H., ~~Bountra, C~~., ~~Edwards, A~~., ~~Oppermann, U~~.C.T.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6i8b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I8B FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of Spindlin1~~ in ~~complex with~~ the ~~inhibitor VinSpinIn~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=H7T:2-[4-[2-[[2-[3-[2-azanyl-5-(cyclopropylmethoxy)-3,3-dimethyl-indol-6-yl]oxypropyl]-1,3-dihydroisoindol-5-yl]oxy]ethyl]-1,2,3-triazol-1-yl]-1-[4-(2-pyrrolidin-1-ylethyl)piperidin-1-yl]ethanone'>H7T</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=6i8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i8b OCA], [http://pdbe.org/6i8b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i8b RCSB], [http://www.ebi.ac.uk/pdbsum/6i8b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i8b ProSAT]</span></td></tr>
-	[[Category: ~~Arrowsmith~~, C.H]]	+	</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: Arrowsmith, C H]]
		+	[[Category: Bountra, C]]
		+	[[Category: Brennan, P E]]
		+	[[Category: Edwards, A]]
	[[Category: Fagan, V]]		[[Category: Fagan, V]]
-	[[Category: Oppermann, U.C.T]]
	[[Category: Johansson, C]]		[[Category: Johansson, C]]
-	[[Category: Brennan, P.E]]
-	[[Category: Edwards, A]]
	[[Category: Krojer, T]]		[[Category: Krojer, T]]
-	[[Category: ~~Bountra~~, C]]	+	[[Category: Oppermann, U C.T]]
-	[[Category: Sorrell, F.J]]	+	[[Category: Sorrell, F J]]
		+	[[Category: Cell cycle]]
		+	[[Category: Epigenetic]]
		+	[[Category: Methyl-arginine]]
		+	[[Category: Methyl-lysine]]
		+	[[Category: Tudor domain]]

OCA: Protected "6i8b" [edit=sysop:move=sysop]

2018-12-02T18:44:18Z

Protected "6i8b" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:44, 2 December 2018

OCA: New page: '''Unreleased structure''' The entry 6i8b is ON HOLD Authors: Johansson, C., Fagan, V., Brennan, P.E., Sorrell, F.J., Krojer, T., Arrowsmith, C.H., Bountra, C., Edwards, A., Oppermann, ...

2018-12-02T18:44:16Z

New page: '''Unreleased structure''' The entry 6i8b is ON HOLD Authors: Johansson, C., Fagan, V., Brennan, P.E., Sorrell, F.J., Krojer, T., Arrowsmith, C.H., Bountra, C., Edwards, A., Oppermann, ...

New page

'''Unreleased structure'''

The entry 6i8b is ON HOLD

Authors: Johansson, C., Fagan, V., Brennan, P.E., Sorrell, F.J., Krojer, T., Arrowsmith, C.H., Bountra, C., Edwards, A., Oppermann, U.C.T.

Description: Crystal structure of Spindlin1 in complex with the inhibitor VinSpinIn
[[Category: Unreleased Structures]]
[[Category: Arrowsmith, C.H]]
[[Category: Fagan, V]]
[[Category: Oppermann, U.C.T]]
[[Category: Johansson, C]]
[[Category: Brennan, P.E]]
[[Category: Edwards, A]]
[[Category: Krojer, T]]
[[Category: Bountra, C]]
[[Category: Sorrell, F.J]]