Crystal Structure and Potential Head-to-Middle Condensation Function of a Z, Z-Farnesyl Diphosphate Synthase

Plants produce a wide variety of secondary metabolites in response to adverse environmental factors. Z, Z-Farnesyl diphosphate (Z, Z-FPP), synthesized by Z, Z-farnesyl diphosphate synthase (zFPS), supports the formation of phytochemicals in wild tomatoes. Here, the crystal structure of N-terminal truncated zFPS (Delta zFPS) was determined. Irregular products including lavandulyl diphosphate and an unknown compound were surprisingly found. Apart from the truncated Nterminus as a functional regulator, structure-based analysis and mutagenesis assays revealed a residue H103 in Delta zFPS as one of the key elements to this irregular function. A series of substrate-enzyme complex structures were obtained from Delta zFPS-H103Y by co-crystallizing with isopentenyl diphosphate, dimethylallyl thiolodiphosphate, or both. Various substrate-binding modes were revealed. The catalytic mechanisms of both the head-to-tail and head-to-middle reactions in Delta zFPS were proposed. Functional switch between the two mechanisms in this enzyme and the essential role played by the flexible Cterminus were elucidated as well.