5j79 - Revision history

OCA at 10:51, 6 September 2023

2023-09-06T10:51:51Z

←Older revision		Revision as of 10:51, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='5j79' size='340' side='right'caption='[[5j79]], [[Resolution\|resolution]] 2.69Å' scene=''>		<StructureSection load='5j79' size='340' side='right'caption='[[5j79]], [[Resolution\|resolution]] 2.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j79]] 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=5J79 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5J79 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j79]] 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=5J79 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J79 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=6GE:4~~-~~METHYL-3-{~~[~~6-(METHYLSULFONYL)QUINOLIN-4-YL~~]~~AMINO}PHENOL'>6GE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.69Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">[~~[5j7b\|5j7b~~]~~]</td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6GE:4-METHYL-3-{[6-(METHYLSULFONYL)QUINOLIN-4-YL]AMINO}PHENOL'>6GE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<~~tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 ([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=5j79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j79 OCA], [https://pdbe.org/5j79 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j79 RCSB], [https://www.ebi.ac.uk/pdbsum/5j79 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j79 ProSAT]</span></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=5j79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j79 OCA], [~~http~~://pdbe.org/5j79 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5j79 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5j79 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5j79 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/RIPK2_HUMAN RIPK2_HUMAN]] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.<ref>PMID:14638696</ref> <ref>PMID:17054981</ref> <ref>PMID:18079694</ref> <ref>PMID:21123652</ref>	+	[https://www.uniprot.org/uniprot/RIPK2_HUMAN RIPK2_HUMAN] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.<ref>PMID:14638696</ref> <ref>PMID:17054981</ref> <ref>PMID:18079694</ref> <ref>PMID:21123652</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Casillas~~, L N~~]]	+	[[Category: Casillas LN]]
-	[[Category: Convery~~, M A~~]]	+	[[Category: Convery MA]]
-	[[Category: Haile~~, P A~~]]	+	[[Category: Haile PA]]
-	[[Category: Lakdawala~~, A S~~]]	+	[[Category: Lakdawala AS]]
-	[[Category: Votta~~, B J]]~~	+	[[Category: Votta BJ]]
-	~~[[Category: Inhibitor selectivity]]~~	+
-	~~[[Category: Kinase domain]]~~	+
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Structure-based drug design]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:31, 10 June 2020

2020-06-10T07:31:55Z

←Older revision		Revision as of 07:31, 10 June 2020
Line 1:		Line 1:

	==The identification and pharmacological characterization of 6-(tert-butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a highly potent and selective inhibitor of RIP2 Kinase, Compound 3 complex==		==The identification and pharmacological characterization of 6-(tert-butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a highly potent and selective inhibitor of RIP2 Kinase, Compound 3 complex==
-	<StructureSection load='5j79' size='340' side='right' caption='[[5j79]], [[Resolution\|resolution]] 2.69Å' scene=''>	+	<StructureSection load='5j79' size='340' side='right'caption='[[5j79]], [[Resolution\|resolution]] 2.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j79]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J79 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5J79 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j79]] 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=5J79 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J79 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6GE:4-METHYL-3-{[6-(METHYLSULFONYL)QUINOLIN-4-YL]AMINO}PHENOL'>6GE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6GE:4-METHYL-3-{[6-(METHYLSULFONYL)QUINOLIN-4-YL]AMINO}PHENOL'>6GE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5j7b\|5j7b]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5j7b\|5j7b]]</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=5j79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j79 OCA], [http://pdbe.org/5j79 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j79 RCSB], [http://www.ebi.ac.uk/pdbsum/5j79 PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 ([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=5j79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j79 OCA], [http://pdbe.org/5j79 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j79 RCSB], [http://www.ebi.ac.uk/pdbsum/5j79 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j79 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Casillas, L N]]		[[Category: Casillas, L N]]
	[[Category: Convery, M A]]		[[Category: Convery, M A]]

OCA at 15:57, 1 June 2016

2016-06-01T15:57:21Z

←Older revision		Revision as of 15:57, 1 June 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 5j79 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==The identification and pharmacological characterization of 6-(tert-butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a highly potent and selective inhibitor of RIP2 Kinase, Compound 3 complex==
		+	<StructureSection load='5j79' size='340' side='right' caption='[[5j79]], [[Resolution\|resolution]] 2.69Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5j79]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J79 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J79 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6GE:4-METHYL-3-{[6-(METHYLSULFONYL)QUINOLIN-4-YL]AMINO}PHENOL'>6GE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5j7b\|5j7b]]</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=5j79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j79 OCA], [http://pdbe.org/5j79 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j79 RCSB], [http://www.ebi.ac.uk/pdbsum/5j79 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RIPK2_HUMAN RIPK2_HUMAN]] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.<ref>PMID:14638696</ref> <ref>PMID:17054981</ref> <ref>PMID:18079694</ref> <ref>PMID:21123652</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines. Recently, several inhibitors of RIP2 kinase have been disclosed that have contributed to the fundamental understanding of the role of RIP2 in this pathway. However, because they lack either broad kinase selectivity or strong affinity for RIP2, these tools have only limited utility to assess the role of RIP2 in complex environments. We present, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Having demonstrated the pharmacological precision of this tool compound, we report its use in elucidating the role of RIP2 kinase in a variety of in vitro, in vivo, and ex vivo experiments, further clarifying our understanding of the role of RIP2 in NOD1 and NOD2 mediated disease pathogenesis.

-	~~Authors~~:	+	The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase.,Haile PA, Votta BJ, Marquis RW, Bury MJ, Mehlmann JF, Singhaus R Jr, Charnley AK, Lakdawala AS, Convery MA, Lipshutz DB, Desai BM, Swift B, Capriotti CA, Berger SB, Mahajan MK, Reilly MA, Rivera EJ, Sun HH, Nagilla R, Beal AM, Finger JN, Cook MN, King BW, Ouellette MT, Totoritis RD, Pierdomenico M, Negroni A, Stronati L, Cucchiara S, Ziolkowski B, Vossenkamper A, MacDonald TT, Gough PJ, Bertin J, Casillas LN J Med Chem. 2016 May 26;59(10):4867-80. doi: 10.1021/acs.jmedchem.6b00211. Epub, 2016 May 4. PMID:27109867<ref>PMID:27109867</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5j79" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Casillas, L N]]
		+	[[Category: Convery, M A]]
		+	[[Category: Haile, P A]]
		+	[[Category: Lakdawala, A S]]
		+	[[Category: Votta, B J]]
		+	[[Category: Inhibitor selectivity]]
		+	[[Category: Kinase domain]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Structure-based drug design]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 15:07, 15 May 2016

2016-05-15T15:07:57Z

←Older revision		Revision as of 15:07, 15 May 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5j79 is ON HOLD	+	The entry 5j79 is ON HOLD until Paper Publication

-	Authors: ~~Convery, M.A., Casillas, L.N., Haile, P.A., Votta, B.J., Lakdawala, A.S.~~	+	Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Lakdawala, A.S]]
-	[[Category: Votta, B.J]]
-	[[Category: Haile, P.A]]
-	[[Category: Casillas, L.N]]
-	[[Category: Convery, M.A]]

OCA: Protected "5j79" [edit=sysop:move=sysop]

2016-05-11T01:36:23Z

Protected "5j79" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:36, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5j79 is ON HOLD Authors: Convery, M.A., Casillas, L.N., Haile, P.A., Votta, B.J., Lakdawala, A.S. Description: Category: Unreleased Structures...

2016-05-11T01:36:22Z

New page: '''Unreleased structure''' The entry 5j79 is ON HOLD Authors: Convery, M.A., Casillas, L.N., Haile, P.A., Votta, B.J., Lakdawala, A.S. Description: Category: Unreleased Structures...

New page

'''Unreleased structure'''

The entry 5j79 is ON HOLD

Authors: Convery, M.A., Casillas, L.N., Haile, P.A., Votta, B.J., Lakdawala, A.S.

Description:
[[Category: Unreleased Structures]]
[[Category: Lakdawala, A.S]]
[[Category: Votta, B.J]]
[[Category: Haile, P.A]]
[[Category: Casillas, L.N]]
[[Category: Convery, M.A]]