7t9v - Revision history

OCA at 09:44, 25 October 2023

OCA — Wed, 25 Oct 2023 09:44:35 GMT

←Older revision		Revision as of 09:44, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7t9v]] 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=7T9V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T9V FirstGlance]. <br>		<table><tr><td colspan='2'>[[7t9v]] 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=7T9V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T9V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GC0:(3S,4S)-4-(3-{5-carbamoyl-2-[(1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)amino]-7-methoxy-1H-benzimidazol-1-yl}propyl)-2-[(1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)amino]-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-8-carboxamide'>GC0</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]] 2.68Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GC0:(3S,4S)-4-(3-{5-carbamoyl-2-[(1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)amino]-7-methoxy-1H-benzimidazol-1-yl}propyl)-2-[(1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)amino]-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-8-carboxamide'>GC0</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=7t9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t9v OCA], [https://pdbe.org/7t9v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t9v RCSB], [https://www.ebi.ac.uk/pdbsum/7t9v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t9v 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=7t9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t9v OCA], [https://pdbe.org/7t9v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t9v RCSB], [https://www.ebi.ac.uk/pdbsum/7t9v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t9v ProSAT]</span></td></tr>
	</table>		</table>

OCA at 09:21, 21 December 2022

OCA — Wed, 21 Dec 2022 09:21:15 GMT

←Older revision		Revision as of 09:21, 21 December 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7t9v is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of hSTING with the agonist, SHR171032==
		+	<StructureSection load='7t9v' size='340' side='right'caption='[[7t9v]], [[Resolution\|resolution]] 2.68Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7t9v]] 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=7T9V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T9V FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GC0:(3S,4S)-4-(3-{5-carbamoyl-2-[(1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)amino]-7-methoxy-1H-benzimidazol-1-yl}propyl)-2-[(1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)amino]-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-8-carboxamide'>GC0</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=7t9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t9v OCA], [https://pdbe.org/7t9v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t9v RCSB], [https://www.ebi.ac.uk/pdbsum/7t9v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t9v 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 ==
		+	Stimulator of interferon genes (STING) activation induces type I interferons and pro-inflammatory cytokines which stimulate tumor antigen cross presentation and the adaptive immune responses against tumor. The first-generation of STING agonists, cyclic di-nucleotide (CDN), mimicked the endogenous STING ligand cyclic guanosine monophosphate adenosine monophosphate, and displayed limited clinical efficacy. Here we report the discovery of SHR1032, a novel small molecule non-CDN STING agonist. Compared to the clinical CDN STING agonist ADU-S100, SHR1032 has much higher activity in human cells with different STING haplotypes and robustly induces interferon beta (IFNbeta) production. When dosed intratumorally, SHR1032 induced strong anti-tumor effects in the MC38 murine syngeneic tumor model. Pharmacodynamic studies showed induction of IFNbeta, tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) in the tumors and, to a lower extent, in the plasma. More importantly, we found SHR1032 directly causes cell death in acute myeloid leukemia (AML) cells. In conclusion, our findings demonstrate that in addition to their established ability to boost anti-tumor immune responses, STING agonists can directly eradicate AML cells, and SHR1032 may present a new and promising therapeutic agent for cancer patients.

-	~~Authors: Chowdhury~~, R., Miller, M.	+	SHR1032, a novel STING agonist, stimulates anti-tumor immunity and directly induces AML apoptosis.,Song C, Liu D, Liu S, Li D, Horecny I, Zhang X, Li P, Chen L, Miller M, Chowdhury R, Issa M, Shen R, Yan Y, Zhang F, Zhang L, Zhang L, Bai C, Feng J, Zhuang L, Zhang R, Li J, Wilkinson H, Liu J, Tao W Sci Rep. 2022 May 20;12(1):8579. doi: 10.1038/s41598-022-12449-1. PMID:35595822<ref>PMID:35595822</ref>

-	~~Description: Crystal structure~~ of ~~hSTING with~~ the ~~agonist, SHR171032~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Chowdhury, R]]	+	<div class="pdbe-citations 7t9v" style="background-color:#fffaf0;"></div>
-	[[Category: Miller, M]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Chowdhury R]]
		+	[[Category: Miller M]]

OCA at 05:27, 27 January 2022

OCA — Thu, 27 Jan 2022 05:27:22 GMT

←Older revision		Revision as of 05:27, 27 January 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7t9v is ON HOLD	+	The entry 7t9v is ON HOLD until Paper Publication

	Authors: Chowdhury, R., Miller, M.		Authors: Chowdhury, R., Miller, M.

OCA: Protected "7t9v" [edit=sysop:move=sysop]

OCA — Wed, 29 Dec 2021 12:05:58 GMT

Protected "7t9v" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:05, 29 December 2021

OCA: New page: '''Unreleased structure''' The entry 7t9v is ON HOLD Authors: Chowdhury, R., Miller, M. Description: Crystal structure of hSTING with the agonist, SHR171032 [[Category: Unreleased Stru...

OCA — Wed, 29 Dec 2021 12:05:56 GMT

New page: '''Unreleased structure''' The entry 7t9v is ON HOLD Authors: Chowdhury, R., Miller, M. Description: Crystal structure of hSTING with the agonist, SHR171032 [[Category: Unreleased Stru...

New page

'''Unreleased structure'''

The entry 7t9v is ON HOLD

Authors: Chowdhury, R., Miller, M.

Description: Crystal structure of hSTING with the agonist, SHR171032
[[Category: Unreleased Structures]]
[[Category: Chowdhury, R]]
[[Category: Miller, M]]