6iim - Revision history

OCA at 09:42, 22 November 2023

2023-11-22T09:42:56Z

←Older revision		Revision as of 09:42, 22 November 2023
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	==USP14 catalytic domain with IU1-206==		==USP14 catalytic domain with IU1-206==
-	<StructureSection load='6iim' size='340' side='right' caption='[[6iim]], [[Resolution\|resolution]] 2.21Å' scene=''>	+	<StructureSection load='6iim' size='340' side='right'caption='[[6iim]], [[Resolution\|resolution]] 2.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6iim]] 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=6IIM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6IIM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6iim]] 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=6IIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IIM FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=A8L:1-[1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl]-2-(4-hydroxypiperidin-1-yl)ethan-1-one'>A8L</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]] 2.21Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6iik\|6iik]]~~, [[~~6iil~~\|~~6iil~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A8L:1-[1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl]-2-(4-hydroxypiperidin-1-yl)ethan-1-one'>A8L</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>USP14, TGT ([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=6iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iim OCA], [https://pdbe.org/6iim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iim RCSB], [https://www.ebi.ac.uk/pdbsum/6iim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iim ProSAT]</span></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase~~ 1~~], with EC number~~ [~~http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=3.~~4~~.19.12~~ 3.4~~.19.12]~~ </~~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=6iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iim OCA], [~~http~~://pdbe.org/6iim PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6iim RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6iim PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6iim ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/UBP14_HUMAN UBP14_HUMAN]] Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs).<ref>PMID:18162577</ref> <ref>PMID:19135427</ref> <ref>PMID:19106094</ref>	+	[https://www.uniprot.org/uniprot/UBP14_HUMAN UBP14_HUMAN] Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs).<ref>PMID:18162577</ref> <ref>PMID:19135427</ref> <ref>PMID:19106094</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6iim" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6iim" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Thioesterase 3D structures\|Thioesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Ubiquitinyl hydrolase 1~~]]	+	[[Category: Large Structures]]
-	[[Category: Mei~~, Z Q~~]]	+	[[Category: Mei ZQ]]
-	[[Category: Wang, F]]	+	[[Category: Wang F]]
-	[[Category: Wang~~, J W~~]]	+	[[Category: Wang JW]]
-	[[Category: Wang~~, Y W]]~~	+	[[Category: Wang YW]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Structural protein]]~~	+
-	~~[[Category: Usp14 inhibitor complex~~]]	+

OCA at 09:05, 19 December 2018

2018-12-19T09:05:10Z

←Older revision		Revision as of 09:05, 19 December 2018
Line 3:		Line 3:
	<StructureSection load='6iim' size='340' side='right' caption='[[6iim]], [[Resolution\|resolution]] 2.21Å' scene=''>		<StructureSection load='6iim' size='340' side='right' caption='[[6iim]], [[Resolution\|resolution]] 2.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6iim]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IIM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6iim]] 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=6IIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IIM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A8L:1-[1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl]-2-(4-hydroxypiperidin-1-yl)ethan-1-one'>A8L</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A8L:1-[1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl]-2-(4-hydroxypiperidin-1-yl)ethan-1-one'>A8L</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6iik\|6iik]], [[6iil\|6iil]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6iik\|6iik]], [[6iil\|6iil]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">USP14, TGT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=6iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iim OCA], [http://pdbe.org/6iim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iim RCSB], [http://www.ebi.ac.uk/pdbsum/6iim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iim 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=6iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iim OCA], [http://pdbe.org/6iim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iim RCSB], [http://www.ebi.ac.uk/pdbsum/6iim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iim ProSAT]</span></td></tr>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Ubiquitinyl hydrolase 1]]		[[Category: Ubiquitinyl hydrolase 1]]
	[[Category: Mei, Z Q]]		[[Category: Mei, Z Q]]

OCA at 06:55, 12 December 2018

2018-12-12T06:55:40Z

←Older revision		Revision as of 06:55, 12 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6iim is ~~ON HOLD~~	+	==USP14 catalytic domain with IU1-206==
		+	<StructureSection load='6iim' size='340' side='right' caption='[[6iim]], [[Resolution\|resolution]] 2.21Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6iim]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IIM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A8L:1-[1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl]-2-(4-hydroxypiperidin-1-yl)ethan-1-one'>A8L</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6iik\|6iik]], [[6iil\|6iil]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=6iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iim OCA], [http://pdbe.org/6iim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iim RCSB], [http://www.ebi.ac.uk/pdbsum/6iim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iim ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/UBP14_HUMAN UBP14_HUMAN]] Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs).<ref>PMID:18162577</ref> <ref>PMID:19135427</ref> <ref>PMID:19106094</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The ubiquitin system is important for drug discovery, and the discovery of selective small-molecule inhibitors of deubiquitinating enzymes (DUBs) remains an active yet extremely challenging task. With a few exceptions, previously developed inhibitors have been found to bind the evolutionarily conserved catalytic centers of DUBs, resulting in poor selectivity. The small molecule IU1 was the first-ever specific inhibitor identified and exhibited surprisingly excellent selectivity for USP14 over other DUBs. However, the molecular mechanism for this selectivity was elusive. Herein, we report the high-resolution co-crystal structures of the catalytic domain of USP14 bound to IU1 and three IU1 derivatives. All the structures of these complexes indicate that IU1 and its analogs bind to a previously unknown steric binding site in USP14, thus blocking the access of the C-terminus of ubiquitin to the active site of USP14 and abrogating USP14 activity. Importantly, this steric site in USP14 is very unique, as suggested by structural alignments of USP14 with several known DUB X-ray structures. These results, in conjunction with biochemical characterization, indicate a coherent steric blockade mechanism for USP14 inhibition by compounds of the IU series. In light of the recent report of steric blockade of USP7 by FT671, this work suggests a potential generally applicable allosteric mechanism for the regulation of DUBs via steric blockade, as showcased by our discovery of IU1-248 which is 10-fold more potent than IU1.

-	~~Authors: Mei, Z.Q~~., Wang, J~~.W.~~, ~~Wang~~, F., Wang, Y.W.	+	Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade.,Wang Y, Jiang Y, Ding S, Li J, Song N, Ren Y, Hong D, Wu C, Li B, Wang F, He W, Wang J, Mei Z Cell Res. 2018 Dec;28(12):1186-1194. doi: 10.1038/s41422-018-0091-x. Epub 2018, Sep 25. PMID:30254335<ref>PMID:30254335</ref>

-	~~Description: USP14 catalytic domain with IU1~~-~~206~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6iim" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Ubiquitinyl hydrolase 1]]
		+	[[Category: Mei, Z Q]]
	[[Category: Wang, F]]		[[Category: Wang, F]]
-	[[Category: Wang, J.W]]	+	[[Category: Wang, J W]]
-	[[Category: Wang, Y.W]]	+	[[Category: Wang, Y W]]
-	[[Category: ~~Mei, Z.Q~~]]	+	[[Category: Hydrolase]]
		+	[[Category: Structural protein]]
		+	[[Category: Usp14 inhibitor complex]]

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

2018-10-17T06:24:32Z

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

←Older revision

Revision as of 06:24, 17 October 2018

OCA: New page: '''Unreleased structure''' The entry 6iim is ON HOLD Authors: Mei, Z.Q., Wang, J.W., Wang, F., Wang, Y.W. Description: USP14 catalytic domain with IU1-206 [[Category: Unreleased Struct...

2018-10-17T06:24:31Z

New page: '''Unreleased structure''' The entry 6iim is ON HOLD Authors: Mei, Z.Q., Wang, J.W., Wang, F., Wang, Y.W. Description: USP14 catalytic domain with IU1-206 [[Category: Unreleased Struct...

New page

'''Unreleased structure'''

The entry 6iim is ON HOLD

Authors: Mei, Z.Q., Wang, J.W., Wang, F., Wang, Y.W.

Description: USP14 catalytic domain with IU1-206
[[Category: Unreleased Structures]]
[[Category: Wang, F]]
[[Category: Wang, J.W]]
[[Category: Wang, Y.W]]
[[Category: Mei, Z.Q]]