Useful Information
Human farnesyl diphosphate synthase (Thr210 to Ser mutatnt bound to risidronate)
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PDB Code 2QIS Target Class Miscellaneous Target FDPS Alias FDPS, FPS Disease Area/Function metabolism, cancer, signalling Date Deposited Jul 05 2007 Authors Related Structure 1YV5, 1ZW5, 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. Here we report the structure of the T210S mutant of FDPS in complex with risedronate. This structure adds to our understanding of the mechanism of inhibition of this important drug target.
