2E8T

S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with magnesium, FsPP and IPP

Summary for 2E8T

• Entry DOI: 10.2210/pdb2e8t/pdb
• Related: 2DH4 2E8U 2E8V 2E8W 2E8X 2E90 2E91 2E92 2E93 2E94 2E95 2E96 2E97
• Descriptor: Geranylgeranyl pyrophosphate synthetase, MAGNESIUM ION, 3-METHYLBUT-3-ENYL TRIHYDROGEN DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: prenyltransferase, farnesyl pyrophosphate, bisphosphonate, transferase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Cytoplasm (By similarity): Q12051
• Total number of polymer chains: 2
• Total formula weight: 79984.31

Authors

Guo, R.T.,Ko, T.P.,Chen, C.K.-M.,Jeng, W.Y.,Chang, T.H.,Liang, P.H.,Oldfield, E.,Wang, A.H.-J. (deposition date: 2007-01-23, release date: 2007-06-12, Last modification date: 2023-10-25)

Primary citation

Guo, R.T.,Cao, R.,Liang, P.H.,Ko, T.P.,Chang, T.H.,Hudock, M.P.,Jeng, W.Y.,Chen, C.K.-M.,Zhang, Y.,Song, Y.,Kuo, C.J.,Yin, F.,Oldfield, E.,Wang, A.H.-J.
Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases
Proc.Natl.Acad.Sci.Usa, 104:10022-10027, 2007

PubMed 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.

PubMed: 17535895
DOI: 10.1073/pnas.0702254104

Experimental method

X-RAY DIFFRACTION (2.13 Å)