Given that 2F-GGPP is functionalized with a fluorine atom at the C2 position of its hydrophobic tail, which impedes the propagation of the generated carbocation , it provides an opportunity to investigate substrate binding and interactions within the active site. We then performed co-crystallization experiments using 2F-GGPP, which led to the acquisition of the co-crystal structure of PcTS1-2F-GGPP-Mg 2+ . This structure was resolved at a 3.5 Å resolution, using the apo-PcTS1 structure as a reference. However, the preliminary modeling of the 2F-GGPP ligand, based on semireliable diffraction data, suggested a less-than-optimal fit. To ensure accuracy, we chose to only present the three Mg 2+ ions, and we referred to the co-crystal structure as PcTS1-Mg 2+ (PDB ID: 8ZWZ, Supplementary Table ). The PcTS1-Mg 2+ structure shows a similar overall structure with apo-PcTS1 (root-mean-square deviation (RMSD) of 0.83 Å for Cα atoms), with a slightly different fold in loop regions, as shown in Figs. .