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Figure 3 | BMC Structural Biology

Figure 3

From: Ternary complex structures of human farnesyl pyrophosphate synthase bound with a novel inhibitor and secondary ligands provide insights into the molecular details of the enzyme’s active site closure

Figure 3

Ligand binding to human FPPS. (A) The active site structures of the FPPS-YS0470-PPi complex (cyan) and the FPPS-zoledronate-IPP complex (white) [PDB: 1ZW5] are presented superimposed. The IPP molecule in the zoledronate complex is not shown for clear visualization of the bisphosphonates. The hydroxyl ‘hook’ of the bound zoledronate is circled in red. This functional group forms a hydrogen bond with the side chain of D243, which is represented as a grey dashed line in the illustration. The orange dashed lines represent stacking interactions between YS0470 and the residues F99 and Q171. (B) ITC isotherms for the binding of PPi and IPP to the human FPPS-YS0470 complex. Three independent experiments were carried out for each ligand. The binding parameters were determined from each data set by using a one-site model. The reported values are Mean ± SEM from the three experiments. T = 303.15 kelvin. (C) A bar graph showing melting temperatures of human FPPS in various ligand-bound states measured by DSF. In order to ensure complete complex formation, YS0470 and the secondary ligands were added at 10- and 100-fold molar excess of the protein, respectively.

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