Useful Information
FDPS: Human Farnesyl Diphosphate Synthase in Complex with Risedronate
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PDB Code 1YV5 Target Class Oxidoreductases Target FDPS-Risedronate Alias FDPS, FPS Disease Area/Function metabolism, cancer Date Deposited Feb 15 2005 Authors Related Structure 1ZW5, 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 isopentenylpyrophosphate 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.Interest in understanding FDPS activity stems from the recent discovery that FDPS is the molecular target of nitrogen-containing bisphosphonates. These compounds disrupt cell growth through FDPS inhibition in parasitic organisms in vitro. In humans, bisphosphonates are targeted to bone tissue where FDPS inhibition in bone-resorbing osteoclasts is a current therapeutic approach for treating post-menopausal osteoporosis. Because of their bone-targeting properties, bisphosphonates have also found use as agents to treat tumor-induced hypercalcemia, Paget's disease, and osteolytic metastases.
