Geranylgeranyl diphosphate-synthase

MATH s K, HEARST J E and pouLTER c D (1992) The crtE gene mErwinia herbicola encodes geranylgeranyl diphosphate synthase , Proc Natl Acad Sci, 89, 6761-4. 

Cervantes-Cervantes, M. et al., Maize cDNAs expressed in endosperm encode functional famesyl diphosphate synthase with geranylgeranyl diphosphate synthase activity, Plant Physiol. 220, 2006. 

Okada, K. et al., Five geranylgeranyl diphosphate synthases expressed in different organs are localized into three subcellular compartments in Arabidopsis, Plant Physiol. 122, 1045, 2000. 

Figure 73. The carotenoid biosynthetic pathway. Enzymes are named according to the designation of their genes Ccs, capsanthin-capsorubin synthase CrtL-b, lycopene-b-cyclase CrtL-e, lycopene-e-cyclase CrtR-b, b-ring hydroxylase, CrtR-e, e-ring hydroxylase DMADP, dimethylallyl diphosphate GGDP, geranylgeranyl diphosphate Ggps, geranylgeranyl-diphosphate synthase IDP, isopentenyl diphosphate Ipi, IDP isomerase Pds, phytoene desaturase Psy, phytoene synthase Vde, violaxanthin de-epoxidase Zds, z-carotene desaturase Zep, zeaxanthin epoxidase. (From van den Berg and others 2000.)...

Fig. 2. Schematic representation of paclitaxel biosynthesis. Dimethylallyl-diphosphate and isopentenyl-diphosphate are condensed through geranylgeranyl diphosphate synthase activity to render geranylgeranyl-diphosphate (GGPP). GGPP is converted into taxa-4(5), 11 (12)-diene in a reaction catalyzed by the taxane synthase (TS). A series of reactions catalyzed by cytochrome P450 monoxygenases lead to the production of a taxane intermediate that is further converted to baccatin III through enzymes-driven oxidation and oxetane ring formation. The side chain moiety of paclitaxel is derived from L-phenylalanine. Three consecutive arrows mean multiple steps. Ac, acetyl Bz, benzoyl.

DIMETHYLALLYLTRANSTRANSFERASE Geranylgeranyl diphosphate synthase, FARNESYLTRANSTRANSFERASE Geranylgeranyltransferases,... 

A Steiger, HJPyun, RM Coates. Synthesis and characterization of aza analog inhibitors of squalene and geranylgeranyl diphosphate synthases. J Org Chem 57 3444-3450, 1992. 

Recently, a key player in the ginkgolide biosynthesis has been isolated and characterized A cDNA that encodes G. biloba levopimaradiene synthase, a diterpene synthase involved in ginkgolide biosynthesis, was isolated and characterized. Similarly, a new geranylgeranyl diphosphate synthase gene from G. biloba, was characterized. ... 

Zhang, Y.H., et al. (2009). Lipophihc bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors an X-ray and NMR investigation. J Am Chem Soc 131 5153-5162. 

Ling, Y., Li, Z.H., Miranda, K., Oldfield, E., and Moreno, S.N. (2007). The farnesyl-diphosphate/geranylgeranyl-diphosphate synthase of Toxoplasma gondii is a bifunctional enzyme and a molecular target of bisphosphonates. J Biol Chem 282 30804—30816. 

Wiemer, A.J., Yu, J.S., Lamb, K.M., Hohl, R.J., and Wiemer, D.F. (2008). Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors. Bioorg Med Chem 16 390-399. 

Laskaris, G., Van Der Heijden, R. and Verpoorte, R. (2000) Purification and partial characterisation of geranylgeranyl diphosphate synthase, from Taxus baccata cell cultures. An enzyme that regulates taxane biosynthesis. Plant Sci., 153, 97-105. 

Schmidt, A. and Gershenzon, J. (2007) Cloning and characterization of isoprenyl diphosphate synthases with famesyl diphosphate and geranylgeranyl diphosphate synthase activity from Norway spruce (Picea abies) and their relation to induced oleoresin formation. Phytochemistry, 68, 2649-59. 

Zenitani, S Tashiro, S Shindo, K Nagai, K Suzuki, K., Imoto, M. (2003). Gerfelin, a novel inhibitor of geranylgeranyl diphosphate synthase from Beau-veriafelina QN22047 1. Taxonomy, fermentation, isolation, and biological activities. J. Antibiot., 56, 617-621. 

Fig. 1.5 Reactions catalyzed by short chain isoprenyl diphosphate synthases in plants. All use the same precursors, IPP and DMAPP, but the enzymes may reside in different subcelLular compartments. The reactions catalyzed by geranyl diphosphate synthase and geranylgeranyl diphosphate synthase are thought to occur in the plastid, and the reaction catalyzed by farnesyl diphosphate in the cytosol.

HEFNER, J., KETCHUM, R.E.B., CROTEAU, R., Cloning and functional expression of a cDNA encoding geranylgeranyl diphosphate synthase from Taxus canadensis and assessment of the role of this prenyltransferase in cells induced for Taxol production., Biochem. Biophys., 1998, 360, 62-74. 

The same research group have reported a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS) by lipophilic bisphosphonates (538-539, 541, 547-549, 550-554). Nuclear magnetic... 

Wiemer AJ, Wiemer DF, Hohl RJ (2011) Geranylgeranyl diphosphate synthase an tanerging therapeutic target Clin Pharmacol Thta- 90 804—812... 

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