View source for 7ssm


==Crystal structure of human STING R232 in complex with compound 11==
<StructureSection load='7ssm' size='340' side='right'caption='[[7ssm]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ssm]] 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=7SSM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SSM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B7L:2-({[(8R)-pyrazolo[1,5-a]pyrimidine-3-carbonyl]amino}methyl)-1-benzofuran-7-carboxylic+acid'>B7L</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=7ssm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ssm OCA], [https://pdbe.org/7ssm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ssm RCSB], [https://www.ebi.ac.uk/pdbsum/7ssm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ssm 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 ==
The identification of agonists of the stimulator of interferon genes (STING) pathway has been an area of intense research due to their potential to enhance innate immune response and tumor immunogenicity in the context of immuno-oncology therapy. Initial efforts to identify STING agonists focused on the modification of 2',3'-cGAMP (1) (an endogenous STING activator ligand) and other closely related cyclic dinucleotides (CDNs). While these efforts have successfully identified novel CDNs that have progressed into the clinic, their utility is currently limited to patients with solid tumors that STING agonists can be delivered to intratumorally. Herein, we report the discovery of a unique class of non-nucleotide small-molecule STING agonists that demonstrate antitumor activity when dosed intratumorally in a syngeneic mouse model.

Discovery of Non-Nucleotide Small-Molecule STING Agonists via Chemotype Hybridization.,Cherney EC, Zhang L, Lo J, Huynh T, Wei D, Ahuja V, Quesnelle C, Schieven GL, Futran A, Locke GA, Lin Z, Monereau L, Chaudhry C, Blum J, Li S, Fereshteh M, Li-Wang B, Gangwar S, Pan C, Chong C, Zhu X, Posy SL, Sack JS, Zhang P, Ruzanov M, Harner M, Akhtar F, Schroeder GM, Vite G, Fink B J Med Chem. 2022 Feb 2. doi: 10.1021/acs.jmedchem.1c01986. PMID:35108011<ref>PMID:35108011</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ssm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Stimulator of interferon genes protein 3D structures|Stimulator of interferon genes protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Critton DA]]
[[Category: Sack JS]]