7ssm

Crystal structure of human STING R232 in complex with compound 11

spinqualitylabelsall models 7ssm, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ssm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.96Å Ligands: B7L Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stimulator of interferon genes protein 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA