5DGM: Crystal Structure Of Human Fpps In Complex With Monophosphonate Compound 7

Targeting drugs to their desired site of action can increase their safety and efficacy. Bisphosphonates are prototypical examples of drugs targeted to bone. However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Furthermore, bisphosphonate bone affinity comes at the expense of very low and variable oral bioavailability. FPPS inhibitors were developed with a monophosphonate as a bone-affinity tag that confers moderate affinity to bone, which can furthermore be tuned to the desired level, and the relationship between structure and bone affinity was evaluated by using an NMR-based bone-binding assay. The concept of targeting drugs to bone with moderate affinity, while retaining oral bioavailability, has broad application to a variety of other bone-targeted drugs.
PDB ID: 5DGMDownload
MMDB ID: 140875
PDB Deposition Date: 2015/8/28
Updated in MMDB: 2016/07
Experimental Method:
x-ray diffraction
Resolution: 2.86  Å
Source Organism:
Similar Structures:
Biological Unit for 5DGM: dimeric; determined by software (PISA)
Molecular Components in 5DGM
Label Count Molecule
Proteins (2 molecules)
Farnesyl Pyrophosphate Synthase(Gene symbol: FDPS)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB