2E8V: S. Cerevisiae Geranylgeranyl Pyrophosphate Synthase In Complex With Product Ggpp (P21)

Citation:
Abstract
Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Here, we show that some bisphosphonates can also inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for antibacterial therapy. Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. In UPPS, there are a total of four binding sites (in five structures). These results are of general interest because they provide the first structures of GGPPS- and UPPS-inhibitor complexes, potentially important drug targets, in addition to revealing a remarkably broad spectrum of binding modes not seen in FPPS inhibition.
PDB ID: 2E8VDownload
MMDB ID: 46095
PDB Deposition Date: 2007/1/23
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2E8V: dimeric; determined by author and by software (PISA)
Molecular Components in 2E8V
Label Count Molecule
Proteins (2 molecules)
2
Geranylgeranyl Pyrophosphate Synthetase(Gene symbol: BTS1)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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