The AGC group of protein kinases comprises several targets for small molecule inhibitors of therapeutic significance. Crystal structure data facilitate the design or improvement of selective inhibitory molecules. Cross-selectivity of kinase inhibitors is often observed among closely related enzymes. Usually an obstacle for inhibitor design, cross-selectivity can be useful to obtain structural data from a related kinase, if not available from the original target. Protein kinase A (PKA), a representative of the AGC kinase group, has been cocrystallized with AGC group inhibitors from diverse chemical groups, thus providing structural information about binding modes, selectivity, and cross-selectivity. "Ersatz" kinases were created by mutating the inhibitor binding site of PKA to resemble other related kinases from the AGC group. The cocrystallization of these ersatz kinases with certain AGC group small molecule inhibitors elucidated some aspects of protein kinase inhibitor selectivity in this group of kinases.