Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs.

  title={Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs.},
  author={Jean-Michel Rondeau and Francis Bitsch and Emmanuelle Bourgier and Martin Geiser and Ren{\'e} Hemmig and Markus Kroemer and Sylvie Lehmann and Paul Ramage and Sebastien Rieffel and Andr{\'e} Strauss and Jonathan R. Green and Wolfgang Jahnke},
  volume={1 2},
To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). By revealing three structural snapshots of the enzyme catalytic cycle, each associated with a… CONTINUE READING
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