Diguanylate cyclase (DGC)

Diguanylate cyclase (DGC) is a crucial bacterial enzyme responsible for the biosynthesis of the cyclic dinucleotide second messenger, cyclic di-GMP (c-di-GMP), by cyclizing two molecules of GTP. DGCs typically contain a conserved GGDEF domain, which is characteristic of this enzyme family. c-di-GMP is a widespread signaling molecule in bacteria that orchestrates a broad range of bacterial behaviors, including the transition between planktonic and sessile (biofilm) lifestyles, flagellar motility, production of virulence factors, cell cycle regulation, and adaptation to various environmental niches. Due to its central role in bacterial physiology and pathogenicity, particularly in the formation of biofilms that contribute to chronic infections and antibiotic resistance, DGC is considered a promising therapeutic target for the development of novel antibacterial agents. The term 'diguanylate kinase' mentioned as an alternative name in some contexts is a general misnomer for this enzyme, as DGC performs a cyclization reaction, not a phosphorylation (kinase) reaction. The degradation of c-di-GMP is catalyzed by diguanylate phosphodiesterases.

Other names

c-di-GMP synthasediguanylate synthase

Inhibitors of diguanylate cyclase prevent the synthesis of the bacterial second messenger cyclic di-GMP (c-di-GMP) from GTP. By reducing intracellular c-di-GMP levels, these inhibitors disrupt c-di-GMP-mediated signaling pathways, thereby altering key bacterial behaviors such as biofilm formation, motility, and virulence factor expression, potentially rendering bacteria more susceptible to host defenses or existing antibiotics.