cyclic-GMP-AMP hydrolase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: cyclic GMP-AMP + 2 H2O = AMP + GMP. [GOC:sp, PMID:25344812, RHEA:58808]

Cyclic-GMP-AMP hydrolase activity is a type of enzymatic activity that specifically catalyzes the hydrolysis of cyclic GMP-AMP (cGAMP), a second messenger molecule. cGAMP plays a crucial role in innate immunity, acting as a potent activator of the stimulator of interferon genes (STING) pathway. This pathway is essential for the recognition of foreign DNA and the subsequent activation of antiviral and anti-inflammatory responses.

Cyclic-GMP-AMP hydrolase enzymes typically belong to the phosphodiesterase family and function by breaking the phosphodiester bond between the GMP and AMP moieties of cGAMP. This hydrolysis reaction results in the formation of GMP and AMP, effectively inactivating cGAMP and attenuating STING signaling.

The precise mechanism of action can vary depending on the specific enzyme, but generally involves the binding of cGAMP to the active site of the enzyme, followed by a series of catalytic events that lead to the cleavage of the phosphodiester bond. The active site often contains conserved amino acid residues that are essential for catalysis and substrate recognition.

The regulation of cyclic-GMP-AMP hydrolase activity is crucial for maintaining proper immune responses. Dysregulation of this activity can contribute to the development of autoimmune disorders and other inflammatory diseases. For example, mutations in the gene encoding cyclic-GMP-AMP hydrolase have been linked to increased susceptibility to certain autoimmune diseases.

In summary, cyclic-GMP-AMP hydrolase activity plays a vital role in regulating innate immunity by hydrolyzing cGAMP, a key activator of the STING pathway. This enzymatic activity helps to control the activation of antiviral and anti-inflammatory responses and prevent excessive inflammation.'
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Proteins (1)

Compounds (8)