5CG6: Neutron crystal structure of human farnesyl pyrophosphate synthase in complex with risedronate and isopentenyl pyrophosphate

Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate to FPP and is known to be a molecular target of osteoporosis drugs, such as risedronate (RIS), which is a nitrogen-containing bisphosphonate. The protonation states and hydration structure of RIS bound to FPPS were determined by neutron protein crystallography, which allows direct visualization of hydrogens and deuteriums. The structure analysis revealed that the phosphate groups of RIS were fully deprotonated with the abnormally decreased pKa, and that the roles of E93 and D264 consisted of canceling the extra negative charges upon the binding of ligands. Collectively, our neutron structures provided insights into the physicochemical properties during the bisphosphonate binding event.
PDB ID: 5CG6Download
MMDB ID: 133360
PDB Deposition Date: 2015/7/9
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction; neutron diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 5CG6: dimeric; determined by author and by software (PISA)
Molecular Components in 5CG6
Label Count Molecule
Proteins (2 molecules)
Farnesyl Pyrophosphate Synthase(Gene symbol: FDPS)
Molecule annotation
Chemicals (10 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB