Target type: molecularfunction
Catalysis of the reaction: ATP + GTP = 2 diphosphate + cyclic G-P(2'-5')A-P(3'-5') (cyclic 2',3' GAMP). [GOC:dph, PMID:23258413, RHEA:42064]
2',3'-cyclic GMP-AMP synthase (cGAS) is a key enzyme in the innate immune response to cytosolic DNA. It catalyzes the synthesis of 2',3'-cyclic GMP-AMP (cGAMP) from ATP and GTP. cGAMP acts as a second messenger that binds to and activates the stimulator of interferon genes (STING) protein. STING is a crucial component of the cGAS-STING pathway, which ultimately leads to the production of type I interferons and other pro-inflammatory cytokines. This pathway is critical for mounting an antiviral response against viral infections and for initiating an inflammatory response to DNA from damaged cells or invading pathogens.
cGAS exhibits a remarkable ability to discriminate between self and non-self DNA, recognizing exogenous DNA as a threat but ignoring host DNA. This selectivity is achieved through the enzyme's distinct structural features and its ability to sense specific characteristics of DNA, such as its length and structure. cGAS binds directly to double-stranded DNA, recognizing its structure and triggering the enzymatic process that synthesizes cGAMP.
The specific molecular function of 2',3'-cyclic GMP-AMP synthase activity encompasses:
* **DNA binding**: cGAS directly interacts with double-stranded DNA, specifically recognizing its structure and triggering the enzymatic process.
* **ATP and GTP binding**: cGAS binds both ATP and GTP, the substrates for cGAMP synthesis.
* **cGAMP synthesis**: cGAS catalyzes the synthesis of cGAMP from ATP and GTP through a complex series of enzymatic reactions.
* **Activation of STING**: cGAMP serves as a second messenger that binds to and activates STING, triggering the downstream signaling cascade.
The overall function of 2',3'-cyclic GMP-AMP synthase activity is to detect the presence of cytosolic DNA and initiate an immune response through the cGAS-STING pathway, ultimately protecting the host from infection and cellular damage.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Cyclic GMP-AMP synthase | A protein MB21D1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N884] | Homo sapiens (human) |
| Cyclic GMP-AMP synthase | A protein MB21D1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N884] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| quinacrine | quinacrine : A member of the class of acridines that is acridine substituted by a chloro group at position 6, a methoxy group at position 2 and a [5-(diethylamino)pentan-2-yl]nitrilo group at position 9. Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2. | acridines; aromatic ether; organochlorine compound; tertiary amino compound | antimalarial; EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor |
| hydroxychloroquine | hydroxychloroquine : An aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2. An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, it is mainly used as the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions. Hydroxychloroquine: A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970) | aminoquinoline; organochlorine compound; primary alcohol; secondary amino compound; tertiary amino compound | anticoronaviral agent; antimalarial; antirheumatic drug; dermatologic drug |
| mangostin | alpha-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3 and 6, a methoxy group at position 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antioxidant, antimicrobial and antitumour activities. mangostin: xanthone from rind of Garcinia mangostana Linn. fruit | aromatic ether; phenols; xanthones | antimicrobial agent; antineoplastic agent; antioxidant; plant metabolite |
| bx795 | BX795: structure in first source | ureas |