2E92

S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with magnesium and BPH-261

2E92 の概要

• エントリーDOI: 10.2210/pdb2e92/pdb
• 関連するPDBエントリー: 2DH4 2E8T 2E8U 2E8V 2E8W 2E8X 2E90 2E91 2E93 2E94 2E95 2E96 2E97
• 分子名称: Geranylgeranyl pyrophosphate synthetase, MAGNESIUM ION, (1-HYDROXY-2-IMIDAZO[1,2-A]PYRIDIN-3-YLETHANE-1,1-DIYL)BIS(PHOSPHONIC ACID), ... (4 entities in total)
• 機能のキーワード: prenyltransferase, farnesyl pyrophosphate, bisphosphonate, transferase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Cytoplasm (By similarity): Q12051
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79339.63

構造登録者

Guo, R.T.,Ko, T.P.,Cao, R.,Jeng, W.Y.,Chen, C.K.-M.,Chang, T.H.,Liang, P.H.,Oldfield, E.,Wang, A.H.-J. (登録日: 2007-01-24, 公開日: 2007-06-12, 最終更新日: 2023-10-25)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.31 Å)