In enzymology, a geranyltranstransferase () is an enzyme that catalyzes the chemical reaction geranyl diphosphate + isopentenyl diphosphate diphosphate + trans,trans-farnesyl diphosphate Thus, the two substrates of this enzyme are geranyl diphosphate (a 10 carbon precursor) and isopentenyl diphosphate (a 5 carbon precursor) whereas its two products are diphosphate and trans,trans-farnesyl diphosphate (a 15 carbon product). This enzyme belongs to the family of transferases, specifically those transferring aryl or alkyl groups other than methyl groups. Nomenclature The systematic name of this enzyme class is geranyl-diphosphate:isopentenyl-diphosphate geranyltranstransferase. Other names in common use include: farnesyl-diphosphate synthase geranyl transferase I prenyltransferase farnesyl pyrophosphate synthetase farnesylpyrophosphate synthetase Common abbreviations include: FPS, FDS, FPPS, and FDPS. Structure The structure and mechanism of farnesyl pyrophosphate synthase (FPPS), a type of geranyltranstransferase, is well characterized. FPPS is a ~30 kDa Mg2+ dependent homodimeric enzyme that synthesizes (E, E)-farnesyl pyrophosphate in a successive manner from two equivalents of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). FPPS adopts a 3-layered α-helical fold characteristic of many prenyltransferases with 11 helices and flexible loops in between. The centrally located helices (α4 and α8) contain conserved aspartate motifs (DDXXD) that participate in substrate binding and catalysis. Motif aspartate residues, water oxygens, and pyrophosphate coordinate three Mg2+in an octahedral manner. The trinuclear Mg2+ complex is critical for binding DMAPP and stabilizing the pyrophosphate leaving group while the growing hydrocarbon tail wedges into a deep hydrophobic pocket. Site-directed mutagenesis studies have shown that the ultimate length of the isoprenoid product is determined by bulky residues (often phenyalanine) at the hydrophobic pocket's base. Mechanism From crystal structures and kinetic assays, it is believed that FPPS catalyzes the condensation reaction in three concerted steps: (1) Ionization, (2) Condensation, and (3) Elimination. In the first step, three Mg2+stabilize the anionic leaving group, pyrophosphate, on dimethylallyl pyrophosphate (DMAPP). The loss of pyrophosphate forms dimethylallyl cation. In the second step, the reactive C3-C5 double bond in isopentyl pyrophosphate (IPP) performs a nucleophilic attack on the previously formed dimethylallyl cation. The final step involves pyrophosphate held in the trinuclear Mg2+ center acting as a catalytic base in an elimination reaction to form geranyl pyrophosphate. A second consecutive round of geranyl pyrophosphate ionization, condensation with IPP, and elimination forms farnesyl pyrophosphate. Function Geranyltranstransferases are an evolutionarily conserved class of enzymes in Archaea, Bacteria, and Eukarya that participate in a broad range of biosynthetic pathways including those of cholesterol, porphyrin, carotenoids, ubiquinone,