Adenylyl cyclase (AC) class IV-like, a subgroup of the CYTH-like superfamily
This subgroup contains class IV ACs and similar proteins. AC catalyzes the conversion of ATP to 3',5'-cyclic AMP (cAMP) and PPi. cAMP is a key signaling molecule which conveys a variety of signals in different cell types. In prokaryotes, cAMP is a catabolite derepression signal which triggers the expression of metabolic pathways including the lactose operon. Six non-homologous classes of ACs have been identified (I-VI). Class IV ACs are found in this group. In bacteria, the gene encoding Class IV AC has been designated cyaB and the protein as AC2. AC-IV occurs in addition to AC-I in bacterial pathogens such as Yersinia pestis (plague disease). The role of AC-IV is unknown but it has been speculated that it may be a factor in pathogenesis, perhaps providing cAMP for a secondary internal signaling function, or for secretion and uptake into host cells, where it may disrupt normal cellular processes. This subgroup belongs to the CYTH/triphosphate tunnel metalloenzyme (TTM)-like superfamily, whose enzymes have a unique active site located within an eight-stranded beta barrel.
Comment:Based on Yersinia pestis AC-I V and similar proteins with structure, on mutation analysis of Clostridium thermocellum TTM, and on NMR titration experiments of mouse ThTPase.
Comment:Putative active site includes binding sites for substrate and divalent cations.
Structure:2FJT_A; Yersinia pestis AC-IV, bound with a sulphate ion, contacts determined at 4A.
Comment:The sulfate ion is thought to be positioned similarly to the alpha-phosphate in the substrate ATP.
Jiyao W et al.(2023). "The conserved domain database in 2023.",