5joh - Revision history

OCA at 19:00, 20 September 2023

OCA — Wed, 20 Sep 2023 19:00:55 GMT

←Older revision		Revision as of 19:00, 20 September 2023
Line 3:		Line 3:
	<StructureSection load='5joh' size='340' side='right'caption='[[5joh]], [[Resolution\|resolution]] 1.99Å' scene=''>		<StructureSection load='5joh' size='340' side='right'caption='[[5joh]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5joh]] is a 1 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=5JOH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5JOH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5joh]] is a 1 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=5JOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JOH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6M3:2-CHLORO-6-[(5S,6S)-6-HYDROXY-6,7,8,9-TETRAHYDRO-5H-IMIDAZO[1,5-A]AZEPIN-5-YL][1,1-BIPHENYL]-3-CARBONITRILE'>6M3</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.99Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">COPS5, CSN5, JAB1 ([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=6M3:2-CHLORO-6-[(5S,6S)-6-HYDROXY-6,7,8,9-TETRAHYDRO-5H-IMIDAZO[1,5-A]AZEPIN-5-YL][1,1-BIPHENYL]-3-CARBONITRILE'>6M3</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5joh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5joh OCA], [~~http~~://pdbe.org/5joh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5joh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5joh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5joh 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=5joh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5joh OCA], [https://pdbe.org/5joh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5joh RCSB], [https://www.ebi.ac.uk/pdbsum/5joh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5joh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CSN5_HUMAN CSN5_HUMAN]] Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2.<ref>PMID:9535219</ref> <ref>PMID:11285227</ref> <ref>PMID:11337588</ref> <ref>PMID:12732143</ref> <ref>PMID:12628923</ref> <ref>PMID:19214193</ref> <ref>PMID:22609399</ref>	+	[https://www.uniprot.org/uniprot/CSN5_HUMAN CSN5_HUMAN] Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2.<ref>PMID:9535219</ref> <ref>PMID:11285227</ref> <ref>PMID:11337588</ref> <ref>PMID:12732143</ref> <ref>PMID:12628923</ref> <ref>PMID:19214193</ref> <ref>PMID:22609399</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Renatus, M]]	+	[[Category: Renatus M]]
-	[[Category: Wiesmann, C]]	+	[[Category: Wiesmann C]]
-	~~[[Category: Cop9 signalosome]]~~	+
-	~~[[Category: Hydroxylase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Metal protease~~]]	+

OCA at 11:31, 17 June 2020

OCA — Wed, 17 Jun 2020 11:31:41 GMT

←Older revision		Revision as of 11:31, 17 June 2020
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	==CRYSTAL STRUCTURE OF CSN5(2-257) IN COMPLEX WITH CNS5i-1b==		==CRYSTAL STRUCTURE OF CSN5(2-257) IN COMPLEX WITH CNS5i-1b==
-	<StructureSection load='5joh' size='340' side='right' caption='[[5joh]], [[Resolution\|resolution]] 1.99Å' scene=''>	+	<StructureSection load='5joh' size='340' side='right'caption='[[5joh]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5joh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JOH OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5JOH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5joh]] is a 1 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=5JOH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JOH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6M3:2-CHLORO-6-[(5S,6S)-6-HYDROXY-6,7,8,9-TETRAHYDRO-5H-IMIDAZO[1,5-A]AZEPIN-5-YL][1,1-BIPHENYL]-3-CARBONITRILE'>6M3</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6M3:2-CHLORO-6-[(5S,6S)-6-HYDROXY-6,7,8,9-TETRAHYDRO-5H-IMIDAZO[1,5-A]AZEPIN-5-YL][1,1-BIPHENYL]-3-CARBONITRILE'>6M3</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5joh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5joh OCA], [http://pdbe.org/5joh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5joh RCSB], [http://www.ebi.ac.uk/pdbsum/5joh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5joh ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">COPS5, CSN5, JAB1 ([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=5joh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5joh OCA], [http://pdbe.org/5joh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5joh RCSB], [http://www.ebi.ac.uk/pdbsum/5joh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5joh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5joh" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5joh" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Signalosome\|Signalosome]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Renatus, M]]		[[Category: Renatus, M]]
	[[Category: Wiesmann, C]]		[[Category: Wiesmann, C]]

OCA at 18:13, 2 November 2016

OCA — Wed, 02 Nov 2016 18:13:19 GMT

←Older revision		Revision as of 18:13, 2 November 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5joh is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==CRYSTAL STRUCTURE OF CSN5(2-257) IN COMPLEX WITH CNS5i-1b==
		+	<StructureSection load='5joh' size='340' side='right' caption='[[5joh]], [[Resolution\|resolution]] 1.99Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5joh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JOH FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6M3:2-CHLORO-6-[(5S,6S)-6-HYDROXY-6,7,8,9-TETRAHYDRO-5H-IMIDAZO[1,5-A]AZEPIN-5-YL][1,1-BIPHENYL]-3-CARBONITRILE'>6M3</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5joh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5joh OCA], [http://pdbe.org/5joh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5joh RCSB], [http://www.ebi.ac.uk/pdbsum/5joh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5joh ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CSN5_HUMAN CSN5_HUMAN]] Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2.<ref>PMID:9535219</ref> <ref>PMID:11285227</ref> <ref>PMID:11337588</ref> <ref>PMID:12732143</ref> <ref>PMID:12628923</ref> <ref>PMID:19214193</ref> <ref>PMID:22609399</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The COP9 signalosome (CSN) is a central component of the activation and remodelling cycle of cullin-RING E3 ubiquitin ligases (CRLs), the largest enzyme family of the ubiquitin-proteasome system in humans. CRLs are implicated in the regulation of numerous cellular processes, including cell cycle progression and apoptosis, and aberrant CRL activity is frequently associated with cancer. Remodelling of CRLs is initiated by CSN-catalysed cleavage of the ubiquitin-like activator NEDD8 from CRLs. Here we describe CSN5i-3, a potent, selective and orally available inhibitor of CSN5, the proteolytic subunit of CSN. The compound traps CRLs in the neddylated state, which leads to inactivation of a subset of CRLs by inducing degradation of their substrate recognition module. CSN5i-3 differentially affects the viability of tumour cell lines and suppresses growth of a human xenograft in mice. Our results provide insights into how CSN regulates CRLs and suggest that CSN5 inhibition has potential for anti-tumour therapy.

-	~~Authors~~:	+	Targeted inhibition of the COP9 signalosome for treatment of cancer.,Schlierf A, Altmann E, Quancard J, Jefferson AB, Assenberg R, Renatus M, Jones M, Hassiepen U, Schaefer M, Kiffe M, Weiss A, Wiesmann C, Sedrani R, Eder J, Martoglio B Nat Commun. 2016 Oct 24;7:13166. doi: 10.1038/ncomms13166. PMID:27774986<ref>PMID:27774986</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5joh" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Renatus, M]]
		+	[[Category: Wiesmann, C]]
		+	[[Category: Cop9 signalosome]]
		+	[[Category: Hydroxylase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Metal protease]]

OCA at 13:38, 1 June 2016

OCA — Wed, 01 Jun 2016 13:38:21 GMT

←Older revision		Revision as of 13:38, 1 June 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Sun, 15 May 2016 15:40:09 GMT

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

←Older revision

Revision as of 15:40, 15 May 2016

OCA: New page: '''Unreleased structure''' The entry 5joh is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Sun, 15 May 2016 15:40:08 GMT

New page: '''Unreleased structure''' The entry 5joh is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5joh is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]