Structural Comparisons of Class I phosphoinositide 3-kinases

Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell growth. One of these kinases, PI3Kα, is frequently mutated in diverse tumor types. The recently determined structure of PI3Kα reveals features that distinguish this enzyme from related lipid kinases. In addition, wild-type PI3Kγ differs from PI3Kα by a substitution identical to a PI3Kα oncogenic mutant (H1047R), explaining differences in the enzymatic activities of the normal α and γ enzymes. Comparison of the PI3K structures also identified structural features that could potentially be exploited for the design of isoform-specific inhibitors.