2OPM: Human Farnesyl Diphosphate Synthase Complexed With Bisphosphonate Bph- 461

Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and protein geranylgeranyl transferase (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Due to dual site targeting and decreased polarity, the compounds have activities far greater than do current bisphosphonate drugs in inhibiting tumor cell growth and invasiveness, both in vitro and in vivo. We explore how these compounds inhibit cell growth and how cell activity can be predicted based on enzyme inhibition data, and using X-ray diffraction, solid state NMR, and isothermal titration calorimetry, we show how these compounds bind to FPPS and/or GGPPS.
PDB ID: 2OPMDownload
MMDB ID: 61159
PDB Deposition Date: 2007/1/29
Updated in MMDB: 2007/12
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2OPM: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 2OPM
Label Count Molecule
Proteins (2 molecules)
Farnesyl Pyrophosphate Synthetase (Fpp Synthetase) (Fps) (Farnesyl Diphosphate Synthetase) [includes: Dimethylallyltranstransferase (EC; Geranyltranstransferase (EC](Gene symbol: FDPS)
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB