0

Crystallization and Preliminary Neutron Diffraction Experiment of Human Farnesyl Pyrophosphate Synthase Complexed With Risedronate

Takeshi Yokoyama, Andreas Ostermann, Mineyuki Mizuguchi, Nobuo Niimura, Tobias E Schrader, Ichiro Tanaka

Acta Crystallogr F Struct Biol Commun. 2014 Apr;70(Pt 4):470-2.

PMID: 24699741

Abstract:

Nitrogen-containing bisphosphonates (N-BPs), such as risedronate and zoledronate, are currently used as a clinical drug for bone-resorption diseases and are potent inhibitors of farnesyl pyrophosphate synthase (FPPS). X-ray crystallographic analyses of FPPS with N-BPs have revealed that N-BPs bind to FPPS with three magnesium ions and several water molecules. To understand the structural characteristics of N-BPs bound to FPPS, including H atoms and hydration by water, neutron diffraction studies were initiated using BIODIFF at the Heinz Maier-Leibnitz Zentrum (MLZ). FPPS-risedronate complex crystals of approximate dimensions 2.8 × 2.5 × 1.5 mm (∼3.5 mm(3)) were obtained by repeated macro-seeding. Monochromatic neutron diffraction data were collected to 2.4 Å resolution with 98.4% overall completeness. Here, the first successful neutron data collection from FPPS in complex with N-BPs is reported.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
ALP7414837 Etidronate disodium hydrate Etidronate disodium hydrate 7414-83-7 (anhydrous) Price
qrcode