Useful Information
FDPS-zoledronate: Human farnesyl diphosphate synthase in complex with zoledronate, isopentenyl pyrophosphate and magnesium
Click on the iSee icon to launch an enhanced annotation with interactive 3D representations and animated transitions. Please note that a web plugin (activeICM) is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available.
PDB Code 1ZW5 Target Class Oxidoreductases Target FDPS-Zoledronate Alias FDPS, FPS Disease Area/Function metabolism, cancer, signalling Date Deposited Jun 03 2005 Authors Related Structure 1YV5, 2QIS, 3B7L, 3CP6
About this structure
A key branch point enzyme of the mevalonate pathway is farnesyl diphosphate synthase (FDPS, FPPS, EC 2.5.1.10 ), a Mg2+-dependent homodimeric enzyme, localized in peroxisomes. FDPS catalyzes the formation of both geranyl and farnesylpyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. Post-translational modification of C-terminal C AAX sequences by covalent attachment of these isoprenyl chains is crucial for intracellular localization and proper function of small GTPases such as Ras, Rac, Rho , and CDC42.Nitrogen-containing bisphosphonates (N-BPs) are known inhibitors of farnesyl diphosphate synthase and are currently used to treat osteoporosis, Paget's disease of the bone, and malignant bone tumors. Bisphosphonate therapy, which inhibits bone resorption, reduces the risk of fracture by 50% within one year. The structure of human FDPS in complex with isopentenyl pyrophosphate, magnesium, and the N-BP zoledronate shows the binding mode for this important class of inhibitors. These results will further the understanding of structure-activity relationships among N-BPs and FDPS, and will enable optimization of their pharmacological potential.
