Figure 2

Structures of human FPPS ternary complexes at the IPP sub-pocket and the ³⁵⁰KRRK³⁵³ tail regions. (A) The cavity of the IPP sub-pocket is filled with ordered water molecules as well as the bound Pi. The water molecules, which are displayed as red spheres, neutralize the surrounding charged residues and also provide structural support via hydrogen bonds (yellow dashes) to this flexible region. The yellow spheres represent the two water molecules present in the FPPS-YS0470 binary complex [PDB: 4DEM] but not in the FPPS-YS0470-Pi ternary complex, and the grey dashes show their interactions with the adjacent entities. (B) The ³⁵⁰KRRK³⁵³ tail is in the same conformation as that previously seen in the FPPS-YS0470 binary complex. Compound YS0470 and Pi are bound deeper in the active site and too far from the C-terminal region to have any direct interaction with the tail residues. (C and E) The phosphate groups of the bound PPi and IPP superpose very well. Other bound water molecules and water-mediated hydrogen bonding interactions are omitted for clarity. We have sub-divided the PPi binding site into the alpha- and beta-sites for easier description. (D and F) The ³⁵⁰KRRK³⁵³ tail is in the fully closed conformation in the both complexes. The grey meshes represent simulated-annealing omit (F_o-F_c) maps contoured at 3.0 sigma level. Carbon atoms are represented in green, cyan, and magenta, for the FPPS-YS0470-Pi, FPPS-YS0470-PPi, and FPPS-YS0470-IPP ternary complexes, respectively. The color schemes for other atoms (red for oxygen; blue for nitrogen; and orange for phosphorous) are consistent throughout all the figures.