ArticleProtein science : a publication of the Protein Society2017
The catalytic mechanism of cyclic GMP-AMP synthase (cGAS) and implications for innate immunity and inhibition.
Article in Protein science : a publication of the Protein Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Review
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies.Journal of translational medicine · 2026Review
- ELISA-Based Enzyme Kinetics Assay for Measuring cGAS Activity.Bio-protocol · 2026Article
- Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application.Chembiochem : a European journal of chemical biology · 2026Review
- Activation of cGAS-STING signaling in senescent cells promotes the aging process by remodeling the functions of the immune system.Biogerontology · 2025Review
- Targeting the cGAS-STING Pathway to Modulate Immune Inflammation in Diabetes and Cardiovascular Complications: Mechanisms and Therapeutic Insights.Current issues in molecular biology · 2025Review
- The cGAS-STING axis: a comprehensive review from immune defense to disease pathogenesis.Immunologic research · 2025Review
- cGAS-STING: mechanisms and therapeutic opportunities.Science China. Life sciences · 2025Review
- Identification and development of cGAS inhibitors and their uses to treat Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Protein palmitoylation: an emerging regulator of inflammatory signaling and diseases.Frontiers in immunology · 2025Review
- Zinc-based radioenhancers to activate tumor radioimmunotherapy by PD-L1 and cGAS-STING pathway.Journal of nanobiotechnology · 2024Article
- Review
- Type I IFN in Glomerular Disease: Scarring beyond the STING.International journal of molecular sciences · 2024Review
- cGAS goes viral: A conserved immune defense system from bacteria to humans.Molecular cell · 2024Review
- Significance of the cGAS-STING Pathway in Health and Disease.International journal of molecular sciences · 2023Review
- STING antagonists, synthesizedRSC medicinal chemistry · 2023Article
- Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases.Archives of pharmacal research · 2023Review
- cGAMP-activated cGAS-STING signaling: its bacterial origins and evolutionary adaptation by metazoans.Nature structural & molecular biology · 2023Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic GMP-AMP synthase (cGAS) is activated by ds-DNA binding to produce the secondary messenger 2',3'-cGAMP. cGAS is an important control point in the innate immune response; dysregulation of the cGAS pathway is linked to autoimmune diseases while targeted stimulation may be of benefit in immunoncology. We report here the structure of cGAS with dinucleotides and small molecule inhibitors, and kinetic studies of the cGAS mechanism. Our structural work supports the understanding of how ds-DNA activates cGAS, suggesting a site for small molecule binders that may cause cGAS activation at physiological ATP concentrations, and an apparent hotspot for inhibitor binding. Mechanistic studies of cGAS provide the first kinetic constants for 2',3'-cGAMP formation, and interestingly, describe a catalytic mechanism where 2',3'-cGAMP may be a minor product of cGAS compared with linear nucleotides.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.