8a2i - Revision history

OCA at 13:36, 1 February 2024

OCA — Thu, 01 Feb 2024 13:36:18 GMT

←Older revision		Revision as of 13:36, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8a2i]] 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=8A2I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A2I FirstGlance]. <br>		<table><tr><td colspan='2'>[[8a2i]] 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=8A2I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A2I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KWF:2-azanyl-9-[(1~{R},6~{R},8~{R},9~{R},10~{S},15~{R},17~{R},18~{R})-8-[4-azanyl-5-(4-naphthalen-2-ylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3,9,12,18-tetrakis(oxidanyl)-3,12-bis(oxidanylidene)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{6,10}]octadecan-17-yl]-3~{H}-purin-6-one'>KWF</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]] 2.16Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KWF:2-azanyl-9-[(1~{R},6~{R},8~{R},9~{R},10~{S},15~{R},17~{R},18~{R})-8-[4-azanyl-5-(4-naphthalen-2-ylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3,9,12,18-tetrakis(oxidanyl)-3,12-bis(oxidanylidene)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{6,10}]octadecan-17-yl]-3~{H}-purin-6-one'>KWF</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=8a2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a2i OCA], [https://pdbe.org/8a2i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a2i RCSB], [https://www.ebi.ac.uk/pdbsum/8a2i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a2i 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=8a2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a2i OCA], [https://pdbe.org/8a2i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a2i RCSB], [https://www.ebi.ac.uk/pdbsum/8a2i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a2i ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 8a2i" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 8a2i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Stimulator of interferon genes protein 3D structures\|Stimulator of interferon genes protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:35, 19 October 2022

OCA — Wed, 19 Oct 2022 19:35:43 GMT

←Older revision		Revision as of 19:35, 19 October 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 8a2i is ~~ON HOLD until Paper~~ Publication	+	==human STING in complex with 2'-3'-cyclic-GMP-7-deaza(4-(2-naphthyl)phenyl)-AMP==
		+	<StructureSection load='8a2i' size='340' side='right'caption='[[8a2i]], [[Resolution\|resolution]] 2.16Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8a2i]] 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=8A2I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A2I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KWF:2-azanyl-9-[(1~{R},6~{R},8~{R},9~{R},10~{S},15~{R},17~{R},18~{R})-8-[4-azanyl-5-(4-naphthalen-2-ylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3,9,12,18-tetrakis(oxidanyl)-3,12-bis(oxidanylidene)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{6,10}]octadecan-17-yl]-3~{H}-purin-6-one'>KWF</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=8a2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a2i OCA], [https://pdbe.org/8a2i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a2i RCSB], [https://www.ebi.ac.uk/pdbsum/8a2i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a2i ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cyclic dinucleotides (CDNs) are second messengers that activate stimulator of interferon genes (STING). The cGAS-STING pathway plays a promising role in cancer immunotherapy. Here, we describe the synthesis of CDNs containing 7-substituted 7-deazapurine moiety. We used mouse cyclic GMP-AMP synthase and bacterial dinucleotide synthases for the enzymatic synthesis of CDNs. Alternatively, 7-(het)aryl 7-deazapurine CDNs were prepared by Suzuki-Miyaura cross-couplings. New CDNs were tested in biochemical and cell-based assays for their affinity to human STING. Eight CDNs showed better activity than 2'3'-cGAMP, the natural ligand of STING. The effect on cytokine and chemokine induction was also evaluated. The best activities were observed for CDNs bearing large aromatic substituents that point above the CDN molecule. We solved four X-ray structures of complexes of new CDNs with human STING. We observed pi-pi stacking interactions between the aromatic substituents and Tyr240 that are involved in the stabilization of CDN-STING complexes.

-	~~Authors: Vavrina~~, Z., ~~Brynda~~, J., ~~Rezacova~~, P.	+	Design, Synthesis, and Biochemical and Biological Evaluation of Novel 7-Deazapurine Cyclic Dinucleotide Analogues as STING Receptor Agonists.,Vavrina Z, Perlikova P, Milisavljevic N, Chevrier F, Smola M, Smith J, Dejmek M, Havlicek V, Budesinsky M, Liboska R, Vanekova L, Brynda J, Boura E, Rezacova P, Hocek M, Birkus G J Med Chem. 2022 Oct 6. doi: 10.1021/acs.jmedchem.2c01305. PMID:36201304<ref>PMID:36201304</ref>

-	~~Description: human STING in complex with 2''-3''-cyclic-GMP~~-7-~~deaza(4-(2-naphthyl)phenyl)-AMP~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Vavrina, Z~~]]	+	<div class="pdbe-citations 8a2i" style="background-color:#fffaf0;"></div>
-	[[Category: Brynda, J]]	+	== References ==
-	[[Category: Rezacova, P]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Brynda J]]
		+	[[Category: Rezacova P]]
		+	[[Category: Vavrina Z]]

OCA at 15:03, 6 July 2022

OCA — Wed, 06 Jul 2022 15:03:42 GMT

←Older revision		Revision as of 15:03, 6 July 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8a2i is ON HOLD	+	The entry 8a2i is ON HOLD until Paper Publication

	Authors: Vavrina, Z., Brynda, J., Rezacova, P.		Authors: Vavrina, Z., Brynda, J., Rezacova, P.

OCA at 07:16, 22 June 2022

OCA — Wed, 22 Jun 2022 07:16:39 GMT

←Older revision		Revision as of 07:16, 22 June 2022
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	Authors: Vavrina, Z., Brynda, J., Rezacova, P.		Authors: Vavrina, Z., Brynda, J., Rezacova, P.

-	Description: human STING in complex with 2'-3'-cyclic-GMP-7-deaza(4-(2-naphthyl)phenyl)-AMP	+	Description: human STING in complex with 2''-3''-cyclic-GMP-7-deaza(4-(2-naphthyl)phenyl)-AMP
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Rezacova, P]]
	[[Category: Vavrina, Z]]		[[Category: Vavrina, Z]]
	[[Category: Brynda, J]]		[[Category: Brynda, J]]
		+	[[Category: Rezacova, P]]

OCA: Protected "8a2i" [edit=sysop:move=sysop]

OCA — Wed, 15 Jun 2022 04:05:34 GMT

Protected "8a2i" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:05, 15 June 2022

OCA: New page: '''Unreleased structure''' The entry 8a2i is ON HOLD Authors: Vavrina, Z., Brynda, J., Rezacova, P. Description: human STING in complex with 2'-3'-cyclic-GMP-7-deaza(4-(2-naphthyl)phen...

OCA — Wed, 15 Jun 2022 04:05:33 GMT

New page: '''Unreleased structure''' The entry 8a2i is ON HOLD Authors: Vavrina, Z., Brynda, J., Rezacova, P. Description: human STING in complex with 2'-3'-cyclic-GMP-7-deaza(4-(2-naphthyl)phen...

New page

'''Unreleased structure'''

The entry 8a2i is ON HOLD

Authors: Vavrina, Z., Brynda, J., Rezacova, P.

Description: human STING in complex with 2'-3'-cyclic-GMP-7-deaza(4-(2-naphthyl)phenyl)-AMP
[[Category: Unreleased Structures]]
[[Category: Rezacova, P]]
[[Category: Vavrina, Z]]
[[Category: Brynda, J]]