The functional mammalian sAC consist of two heterologous catalytic domains (C1 and C2), forming the 50 kDa amino terminus of the protein. The additional ~140 kDa C terminus of the enzyme includes an autoinhibitory region, canonical P-loop, potential heme-binding domain, and leucine zipper-like sequence, which are a form of putative regulatory domains.
A truncated form of the enzyme only includes the C1 and C2 domains and it is refers to as the minimal functional sAC variant. This sAC-truncated form has cAMP-forming activity much higher than its full-length type. These sAC variants are stimulated by HCO3- and respond to all known selective sAC inhibitors. Crystal structures of this sAC variant comprising only the catalytic core, in apo form and in as complex with various substrate analogs, products, and regulators, reveal a generic Class III AC architecture with sAC-specific features. The structurally related domains C1 and C2 form the typical pseudo-heterodimer, with one active site. The pseudo-symmetric site accommodates the sAC-specific activator HCO3−, which activates by triggering a rearrangement of Arg176, a residue connecting both sites. The anionic sAC inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) acts as a blocker for the entrance to active site and bicarbonate binding pocket.