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It has been possible to determine the 2.2 angstrom X-ray crystallographic structure of the catalytic subunit of PI3K-gamma, the class I enzyme that is activated by heterotrimeric G-protein beta-gamma subunits and Ras. The subunit contains all of the homology regions present in class I PI3Ks, and its catalytic activity is similar to that of the full-length enzyme. The enzyme has a modular structure made up of four domains: a C2 domain, a Ras-binding domain, a catalytic domain and a helical domain. This research forms a basis for mutagenesis and detailed kinetic studies.

Phosphoinositide-specific phospholipase C (PI-PLC) -delta-1 contains a PH domain, an EF-hand domain, a triosephosphate isomerase-like (TIM) -barrel domain, and a C2 domain. The catalytic region is composed of the X and Y domains similar to those in mammalian phospholipases. The active site is present on the C2 domain and is surrounded by a hydrophobic border. The active-site residues taking part in substrate and catalytic calcium binding are conserved in all PI-PLC isozymes. This indicates an evolutionary relation between calcium control and phosphatidylinositol-4,5-bisphosphate hydrolysis.