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.

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

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3D Structures of geranylgeranyl pyrophosphate synthase3D Structures of geranylgeranyl pyrophosphate synthase

Updated on 20-October-2017

2dh4 – yGGPPS + Mg - yeast
2e8t – yGGPPS + Mg + isopentenyl pyrophosphate + farnesyl thiopyrophosphate
2e8u, 2e8w – yGGPPS + Mg + isopentenyl pyrophosphate
2e8v – yGGPPS + GGPP
2z4v – yGGPPS + GGPP + Mg
2e8x – yGGPPS + GPP + Mg
2e90 – yGGPPS + Mg + PP + farnesyl pyrophosphate
2e91, 2e92, 2e93, 2e94, 2e95, 2z7h, 2z4w, 2z4x, 2z4y, 2z4z, 2z50, 2z52, 2z78, 2z7i, 2zeu – yGGPPS + Mg + inhibitor
2zev – yGGPPS + Mg + isopentenyl pyrophosphate + inhibitor
2q80 – GGPPS + GGPP + Mg - human
2azj – SsGGPPS – Sulfolobus solfataricus
2azk – SsGGPPS (mutant)
3lk5, 3lmd – CgGGPPS – Corynebacterium glutamicum
3q2q – CgGGPPS + Ca + isoprenyl diphosphate
3qqv – CgGGPPS + Mg + isoprenyl diphosphate
3n3d, 3pko – GGPPS – Lactobacillus brevis
2j1o – SaGGPPS – Sinapis alba
2j1p – SaGGPPS + GGPP
5e8h – AtGGPPS-3 – Arabidopsis thaliana
5e8k – AtGGPPS-10
5e8l – AtGGPPS-11

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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

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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