Geranylgeranyl pyrophosphate synthase

Function

Geranylgeranyl pyrophosphate synthase (GGPPS) catalyzes the synthesis of geranylgeranyl pyrophosphate (GGPP) from farnesyl diphosphate and isopentenyl diphosphate. GGPPS is involved in the addition of hydrophobic molecules to proteins and in the regulation of a nuclear hormone receptor^[1].

Relevance

GGPPS inhibitors are studied as therapeutical targets since geranylgeranylation is a post-translational modification of several proteins involved in human disease^[2].

Structural highlights

^[3]. Water molecules shown as red spheres.

3D Structures of geranylgeranyl pyrophosphate synthase

Geranylgeranyl pyrophosphate synthase 3D structures

Geranylgeranyl pyrophosphate synthase dimer complex with GGPP and Mg+2 (green) 2z4v

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Croteau R, Purkett PT. Geranyl pyrophosphate synthase: characterization of the enzyme and evidence that this chain-length specific prenyltransferase is associated with monoterpene biosynthesis in sage (Salvia officinalis). Arch Biochem Biophys. 1989 Jun;271(2):524-35. PMID:2730002
↑ Wiemer AJ, Wiemer DF, Hohl RJ. Geranylgeranyl diphosphate synthase: an emerging therapeutic target. Clin Pharmacol Ther. 2011 Dec;90(6):804-12. doi: 10.1038/clpt.2011.215. Epub 2011, Nov 2. PMID:22048229 doi:http://dx.doi.org/10.1038/clpt.2011.215
↑ K-M Chen C, Hudock MP, Zhang Y, Guo RT, Cao R, No JH, Liang PH, Ko TP, Chang TH, Chang SC, Song Y, Axelson J, Kumar A, Wang AH, Oldfield E. Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation. J Med Chem. 2008 Sep 25;51(18):5594-607. PMID:18800762 doi:10.1021/jm800325y

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Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Croteau R, Purkett PT. Geranyl pyrophosphate synthase: characterization of the enzyme and evidence that this chain-length specific prenyltransferase is associated with monoterpene biosynthesis in sage (Salvia officinalis). Arch Biochem Biophys. 1989 Jun;271(2):524-35. PMID:2730002

[2] Wiemer AJ, Wiemer DF, Hohl RJ. Geranylgeranyl diphosphate synthase: an emerging therapeutic target. Clin Pharmacol Ther. 2011 Dec;90(6):804-12. doi: 10.1038/clpt.2011.215. Epub 2011, Nov 2. PMID:22048229 doi:http://dx.doi.org/10.1038/clpt.2011.215

[3] K-M Chen C, Hudock MP, Zhang Y, Guo RT, Cao R, No JH, Liang PH, Ko TP, Chang TH, Chang SC, Song Y, Axelson J, Kumar A, Wang AH, Oldfield E. Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation. J Med Chem. 2008 Sep 25;51(18):5594-607. PMID:18800762 doi:10.1021/jm800325y

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