5ng0 - Revision history

OCA at 12:54, 15 November 2023

OCA — Wed, 15 Nov 2023 12:54:46 GMT

←Older revision		Revision as of 12:54, 15 November 2023
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	<StructureSection load='5ng0' size='340' side='right'caption='[[5ng0]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5ng0' size='340' side='right'caption='[[5ng0]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ng0]] 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=5NG0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NG0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ng0]] 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=5NG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NG0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</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]] 2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5ng0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ng0 OCA], [~~http~~://pdbe.org/5ng0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ng0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ng0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ng0 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=5ng0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ng0 OCA], [https://pdbe.org/5ng0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ng0 RCSB], [https://www.ebi.ac.uk/pdbsum/5ng0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ng0 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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cusack, S]]	+	[[Category: Cusack S]]
-	[[Category: Pellegrini, E]]	+	[[Category: Pellegrini E]]
-	~~[[Category: Active state]]~~	+
-	~~[[Category: Amppcpp]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Rip2k]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:44, 16 October 2019

OCA — Wed, 16 Oct 2019 06:44:08 GMT

←Older revision		Revision as of 06:44, 16 October 2019
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	==Structure of RIP2K(L294F) with bound AMPPCP==		==Structure of RIP2K(L294F) with bound AMPPCP==
-	<StructureSection load='5ng0' size='340' side='right' caption='[[5ng0]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5ng0' size='340' side='right'caption='[[5ng0]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5ng0]] 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=5NG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NG0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ng0]] 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=5NG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NG0 FirstGlance]. <br>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cusack, S]]		[[Category: Cusack, S]]
	[[Category: Pellegrini, E]]		[[Category: Pellegrini, E]]

OCA at 07:42, 6 December 2017

OCA — Wed, 06 Dec 2017 07:42:27 GMT

←Older revision		Revision as of 07:42, 6 December 2017
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	== 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>		[[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 ==
		+	Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K) is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles. The active state has Helix alphaC inwardly displaced and the phosphorylated Activation Segment (AS) disordered, whilst in the inactive state Helix alphaC is outwardly displaced and packed against the helical, non-phosphorylated AS. Biophysical measurements show that the active state is a stable dimer whilst the inactive kinase is in a monomer-dimer equilibrium, consistent with the observed structural differences at the dimer interface. We conclude that RIP2 kinase auto-phosphorylation is intimately coupled to dimerization, similar to the case of BRAF. Our results will help drug design efforts targeting RIP2 as a potential treatment for NOD2-RIP2 related inflammatory diseases.
		+
		+	Structures of the inactive and active states of RIP2 kinase inform on the mechanism of activation.,Pellegrini E, Signor L, Singh S, Boeri Erba E, Cusack S PLoS One. 2017 May 18;12(5):e0177161. doi: 10.1371/journal.pone.0177161., eCollection 2017. PMID:28545134<ref>PMID:28545134</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5ng0" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:50, 16 November 2017

OCA — Thu, 16 Nov 2017 10:50:30 GMT

←Older revision		Revision as of 10:50, 16 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ng0 is ~~ON HOLD until Paper Publication~~	+	==Structure of RIP2K(L294F) with bound AMPPCP==
-		+	<StructureSection load='5ng0' size='340' side='right' caption='[[5ng0]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~: ~~Pellegrini~~, E., ~~Cusack~~, S.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5ng0]] 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=5NG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NG0 FirstGlance]. <br>
-	~~Description~~: ~~Structure~~ of ~~RIP2K~~(~~L294F~~) ~~with bound AMPPCP~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ng0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ng0 OCA], [http://pdbe.org/5ng0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ng0 RCSB], [http://www.ebi.ac.uk/pdbsum/5ng0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ng0 ProSAT]</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Cusack, S]]		[[Category: Cusack, S]]
	[[Category: Pellegrini, E]]		[[Category: Pellegrini, E]]
		+	[[Category: Active state]]
		+	[[Category: Amppcpp]]
		+	[[Category: Kinase]]
		+	[[Category: Rip2k]]
		+	[[Category: Transferase]]

OCA at 08:54, 10 May 2017

OCA — Wed, 10 May 2017 08:54:32 GMT

←Older revision		Revision as of 08:54, 10 May 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ng0 is ON HOLD	+	The entry 5ng0 is ON HOLD until Paper Publication

	Authors: Pellegrini, E., Cusack, S.		Authors: Pellegrini, E., Cusack, S.

OCA: Protected "5ng0" [edit=sysop:move=sysop]

OCA — Wed, 05 Apr 2017 10:04:45 GMT

Protected "5ng0" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:04, 5 April 2017

OCA: New page: '''Unreleased structure''' The entry 5ng0 is ON HOLD Authors: Pellegrini, E., Cusack, S. Description: Structure of RIP2K(L294F) with bound AMPPCP Category: Unreleased Structures [[...

OCA — Wed, 05 Apr 2017 10:04:44 GMT

New page: '''Unreleased structure''' The entry 5ng0 is ON HOLD Authors: Pellegrini, E., Cusack, S. Description: Structure of RIP2K(L294F) with bound AMPPCP Category: Unreleased Structures [[...

New page

'''Unreleased structure'''

The entry 5ng0 is ON HOLD

Authors: Pellegrini, E., Cusack, S.

Description: Structure of RIP2K(L294F) with bound AMPPCP
[[Category: Unreleased Structures]]
[[Category: Cusack, S]]
[[Category: Pellegrini, E]]