The binding and cyclizing of adenosine 5’ triphosphate (ATP) to the catalytic active site of the enzyme is coordinated by two metal cations. The catalytic activity of sAC is increase by the presence of manganese [Mn]. sAC magnesium [Mg] activity is regulated by calcium [Ca] which increases the affinity for ATP of mammalian sAC. In addition, bicarbonate [HCO] releases ATP-Mg substrate inhibition and increases V of the enzyme.
The open conformation state of sAC is reached when ATP, with Ca bound to its γ-phosphate binds with specific residues in the catalytic center of the enzyme. When the second metal – a Mg ion – binds to the α-phosphate of ATP leads to a conformational change of the enzyme: the close state. The change in conformation from open to close state induces esterification of the α-phosphate with the ribose in adenosine and the release of the β- and γ-phosphates, this leads to cyclizing.  Hydrogencarbonate stimulates the enzyme’s V by promoting the allosteric change that leads to active site closure, recruitment of the catalytic Mg ion, and readjustment of the phosphates in the bound ATP. The activator bicarbonate binds to a site pseudo-symmetric to the active site and triggers conformational changes by recruiting Arg176 from the active site (see above - "structure"). Calcium increases substrate affinity by replacing the magnesium in the ion B site, which provides an anchoring point for the beta- and gamma-phosphates of the ATP substrate.