4qxo - Revision history

OCA at 12:49, 1 March 2024

OCA — Fri, 01 Mar 2024 12:49:01 GMT

←Older revision		Revision as of 12:49, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qxo]] 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=4QXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QXO FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qxo]] 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=4QXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QXO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</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]] 1.88Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [https://pdbe.org/4qxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [https://www.ebi.ac.uk/pdbsum/4qxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxo 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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [https://pdbe.org/4qxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [https://www.ebi.ac.uk/pdbsum/4qxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/STING_HUMAN STING_HUMAN] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:21074459</ref> <ref>PMID:21947006</ref> <ref>PMID:23258412</ref>		[https://www.uniprot.org/uniprot/STING_HUMAN STING_HUMAN] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:21074459</ref> <ref>PMID:21947006</ref> <ref>PMID:23258412</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The drug DMXAA (5,6-dimethylxanthenone-4-acetic acid) showed therapeutic promise against solid tumors in mouse models but subsequently failed in human clinical trials. DMXAA was later discovered to activate mouse, but not human, STING, an adaptor protein in the cyclic dinucleotide cGAMP-mediated signaling pathway, inducing type I interferon expression. To facilitate the development of compounds that target human STING, we combined structural, biophysical, and cellular assays to study mouse and human chimeric proteins and their interaction with DMXAA. We identified a single substitution (G230I) that enables a DMXAA-induced conformational transition of hSTING from an inactive "open" to an active "closed" state. We also identified a substitution within the binding pocket (Q266I) that cooperates with G230I and the previously identified S162A binding-pocket point substitution, rendering hSTING highly sensitive to DMXAA. These findings should facilitate the reciprocal engineering of DMXAA analogs that bind and stimulate wild-type hSTING and their exploitation for vaccine-adjuvant and anticancer drug development.
-
-	Binding-Pocket and Lid-Region Substitutions Render Human STING Sensitive to the Species-Specific Drug DMXAA.,Gao P, Zillinger T, Wang W, Ascano M, Dai P, Hartmann G, Tuschl T, Deng L, Barchet W, Patel DJ Cell Rep. 2014 Sep 3. pii: S2211-1247(14)00673-1. doi:, 10.1016/j.celrep.2014.08.010. PMID:25199835<ref>PMID:25199835</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4qxo" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 13:58, 22 February 2023

OCA — Wed, 22 Feb 2023 13:58:17 GMT

←Older revision		Revision as of 13:58, 22 February 2023
Line 3:		Line 3:
	<StructureSection load='4qxo' size='340' side='right'caption='[[4qxo]], [[Resolution\|resolution]] 1.88Å' scene=''>		<StructureSection load='4qxo' size='340' side='right'caption='[[4qxo]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qxo]] 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=4QXO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QXO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qxo]] 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=4QXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QXO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [https://pdbe.org/4qxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [https://www.ebi.ac.uk/pdbsum/4qxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxo ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TMEM173, ERIS, MITA, STING ([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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [~~http~~://pdbe.org/4qxo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qxo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxo ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/STING_HUMAN STING_HUMAN]] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:21074459</ref> <ref>PMID:21947006</ref> <ref>PMID:23258412</ref>	+	[https://www.uniprot.org/uniprot/STING_HUMAN STING_HUMAN] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:21074459</ref> <ref>PMID:21947006</ref> <ref>PMID:23258412</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
-	*[[Stimulator of interferon genes\|Stimulator of interferon genes]]	+	*[[Stimulator of interferon genes protein\|Stimulator of interferon genes protein]]
		+	*[[Stimulator of interferon genes protein 3D structures\|Stimulator of interferon genes protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gao, P]]	+	[[Category: Gao P]]
-	[[Category: Patel~~, D J]]~~	+	[[Category: Patel DJ]]
-	~~[[Category: Cgamp binding]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Innate immunity]]~~	+
-	~~[[Category: Membrane~~]]	+

OCA at 08:59, 24 April 2019

OCA — Wed, 24 Apr 2019 08:59:08 GMT

←Older revision		Revision as of 08:59, 24 April 2019
Line 1:		Line 1:

	==Crystal structure of hSTING(group2) in complex with DMXAA==		==Crystal structure of hSTING(group2) in complex with DMXAA==
-	<StructureSection load='4qxo' size='340' side='right' caption='[[4qxo]], [[Resolution\|resolution]] 1.88Å' scene=''>	+	<StructureSection load='4qxo' size='340' side='right'caption='[[4qxo]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qxo]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qxo]] 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=4QXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TMEM173, ERIS, MITA, STING ([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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://pdbe.org/4qxo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxo 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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://pdbe.org/4qxo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxo ProSAT]</span></td></tr>
	</table>		</table>
Line 26:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Gao, P]]		[[Category: Gao, P]]
	[[Category: Patel, D J]]		[[Category: Patel, D J]]

OCA at 01:39, 5 August 2016

OCA — Fri, 05 Aug 2016 01:39:49 GMT

←Older revision		Revision as of 01:39, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of hSTING(group2) in complex with DMXAA==		==Crystal structure of hSTING(group2) in complex with DMXAA==
	<StructureSection load='4qxo' size='340' side='right' caption='[[4qxo]], [[Resolution\|resolution]] 1.88Å' scene=''>		<StructureSection load='4qxo' size='340' side='right' caption='[[4qxo]], [[Resolution\|resolution]] 1.88Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://pdbe.org/4qxo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4qxo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Stimulator of interferon genes\|Stimulator of interferon genes]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:46, 25 December 2014

OCA — Thu, 25 Dec 2014 14:46:42 GMT

←Older revision		Revision as of 14:46, 25 December 2014
Line 7:		Line 7:
	<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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/STING_HUMAN STING_HUMAN]] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:21074459</ref> <ref>PMID:21947006</ref> <ref>PMID:23258412</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Gao, P.]]	+	[[Category: Gao, P]]
-	[[Category: Patel, D J.]]	+	[[Category: Patel, D J]]
	[[Category: Cgamp binding]]		[[Category: Cgamp binding]]
	[[Category: Immune system]]		[[Category: Immune system]]
	[[Category: Innate immunity]]		[[Category: Innate immunity]]
	[[Category: Membrane]]		[[Category: Membrane]]

OCA at 05:34, 8 October 2014

OCA — Wed, 08 Oct 2014 05:34:51 GMT

←Older revision		Revision as of 05:34, 8 October 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qxo]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXO FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qxo]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXO FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</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=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</span></td></tr>
-	<table>	+	</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 06:00, 24 September 2014

OCA — Wed, 24 Sep 2014 06:00:51 GMT

←Older revision		Revision as of 06:00, 24 September 2014
Line 7:		Line 7:
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</span></td></tr>		<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</span></td></tr>
	<table>		<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The drug DMXAA (5,6-dimethylxanthenone-4-acetic acid) showed therapeutic promise against solid tumors in mouse models but subsequently failed in human clinical trials. DMXAA was later discovered to activate mouse, but not human, STING, an adaptor protein in the cyclic dinucleotide cGAMP-mediated signaling pathway, inducing type I interferon expression. To facilitate the development of compounds that target human STING, we combined structural, biophysical, and cellular assays to study mouse and human chimeric proteins and their interaction with DMXAA. We identified a single substitution (G230I) that enables a DMXAA-induced conformational transition of hSTING from an inactive "open" to an active "closed" state. We also identified a substitution within the binding pocket (Q266I) that cooperates with G230I and the previously identified S162A binding-pocket point substitution, rendering hSTING highly sensitive to DMXAA. These findings should facilitate the reciprocal engineering of DMXAA analogs that bind and stimulate wild-type hSTING and their exploitation for vaccine-adjuvant and anticancer drug development.
		+
		+	Binding-Pocket and Lid-Region Substitutions Render Human STING Sensitive to the Species-Specific Drug DMXAA.,Gao P, Zillinger T, Wang W, Ascano M, Dai P, Hartmann G, Tuschl T, Deng L, Barchet W, Patel DJ Cell Rep. 2014 Sep 3. pii: S2211-1247(14)00673-1. doi:, 10.1016/j.celrep.2014.08.010. PMID:25199835<ref>PMID:25199835</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 10:15, 10 September 2014

OCA — Wed, 10 Sep 2014 10:15:22 GMT

←Older revision		Revision as of 10:15, 10 September 2014
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Crystal structure of hSTING(group2) in complex with DMXAA==
-		+	<StructureSection load='4qxo' size='340' side='right' caption='[[4qxo]], [[Resolution\|resolution]] 1.88Å' scene=''>
-	~~The entry~~ 4qxo is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4qxo]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXO FirstGlance]. <br>
-	~~Authors~~: Gao, P., Patel, D.J.	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene><br>
-		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qxp\|4qxp]], [[4qxq\|4qxq]], [[4qxr\|4qxr]]</td></tr>
-	~~Description~~: ~~Group2~~	+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxo RCSB], [http://www.ebi.ac.uk/pdbsum/4qxo PDBsum]</span></td></tr>
		+	<table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Gao, P.]]
		+	[[Category: Patel, D J.]]
		+	[[Category: Cgamp binding]]
		+	[[Category: Immune system]]
		+	[[Category: Innate immunity]]
		+	[[Category: Membrane]]

OCA at 01:13, 7 August 2014

OCA — Thu, 07 Aug 2014 01:13:49 GMT

←Older revision		Revision as of 01:13, 7 August 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4qxo is ON HOLD	+	The entry 4qxo is ON HOLD until Paper Publication

	Authors: Gao, P., Patel, D.J.		Authors: Gao, P., Patel, D.J.

-	Description: ~~group2~~	+	Description: Group2

OCA: Protected "4qxo" [edit=sysop:move=sysop]

OCA — Wed, 30 Jul 2014 07:05:43 GMT

Protected "4qxo" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:05, 30 July 2014