Useful Information
Human farnesyl diphosphate synthase in complex with minodronate
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PDB Code 3B7L Target Class Miscellaneous Target FDPS + minodronate Alias FDPS, FPS Disease Area/Function metabolism, signalling Date Deposited Oct 31 2007 Authors Related Structure 1YV5, 1ZW5, 2QIS, 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. Minodronate is a clinically used bisphosphonate and is almost certainly the most potent clinically relevant inhibitor of FDPS. An understanding of the mode of binding of Minodronate to FDPS adds to our understanding of the mechanism of inhibition of this important drug target.
