Shown are structural differences in the active sites of CrISY (A) and AmISY (B). A homology model of AmISY was constructed using the previously reported crystal structure of CrISY (PDB code 5DF1, Ref. 25) in complex with geranic acid (GEA, pink sticks) and NADP+ (cyan sticks). All binding pocket residues mutated in an attempt to invert the specificity of CrISY (supplemental Table S2) and the catalytic, conserved Tyr-178 are shown as sticks. The protein backbone is shown as a light gray tube.