Interconversion of the Product Specificity of Type I Eubacterial Farnesyl Diphosphate Synthase and Geranylgeranyl Diphosphate Synthase through One Amino Acid Substitution

2003 ◽  
Vol 133 (1) ◽  
pp. 83-91 ◽  
Author(s):  
T. Kawasaki
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Type I ◽  
Geranylgeranyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate ◽  
Product Specificity

scholarly journals Maize cDNAs Expressed in Endosperm Encode Functional Farnesyl Diphosphate Synthase with Geranylgeranyl Diphosphate Synthase Activity

2006 ◽  
Vol 141 (1) ◽  
pp. 220-231 ◽  
Author(s):  
Miguel Cervantes-Cervantes ◽  
Cynthia E. Gallagher ◽  
Changfu Zhu ◽  
Eleanore T. Wurtzel
Keyword(s):  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate

scholarly journals Geranylgeranyl Diphosphate Synthase in Fission Yeast Is a Heteromer of Farnesyl Diphosphate Synthase (FPS), Fps1, and an FPS-like Protein, Spo9, Essential for Sporulation

2007 ◽  
Vol 18 (9) ◽  
pp. 3568-3581 ◽  
Author(s):  
Yanfang Ye ◽  
Makoto Fujii ◽  
Aiko Hirata ◽  
Makoto Kawamukai ◽  
Chikashi Shimoda ◽  
...  
Keyword(s):  
Membrane Vesicles ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Temperature Sensitive ◽  
Deficient Mutant ◽  
Geranylgeranyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate ◽  
Protein Prenylation ◽  
E Coli ◽  
Farnesylated Protein

Both farnesyl diphosphate synthase (FPS) and geranylgeranyl diphosphate synthase (GGPS) are key enzymes in the synthesis of various isoprenoid-containing compounds and proteins. Here, we describe two novel Schizosaccharomyces pombe genes, fps1+and spo9+, whose products are similar to FPS in primary structure, but whose functions differ from one another. Fps1 is essential for vegetative growth, whereas, a spo9 null mutant exhibits temperature-sensitive growth. Expression of fps1+, but not spo9+, suppresses the lethality of a Saccharomyces cerevisiae FPS-deficient mutant and also restores ubiquinone synthesis in an Escherichia coli ispA mutant, which lacks FPS activity, indicating that S. pombe Fps1 in fact functions as an FPS. In contrast to a typical FPS gene, no apparent GGPS homologues have been found in the S. pombe genome. Interestingly, although neither fps1+nor spo9+expression alone in E. coli confers clear GGPS activity, coexpression of both genes induces such activity. Moreover, the GGPS activity is significantly reduced in the spo9 mutant. In addition, the spo9 mutation perturbs the membrane association of a geranylgeranylated protein, but not that of a farnesylated protein. Yeast two-hybrid and coimmunoprecipitation analyses indicate that Fps1 and Spo9 physically interact. Thus, neither Fps1 nor Spo9 alone functions as a GGPS, but the two proteins together form a complex with GGPS activity. Because spo9 was originally identified as a sporulation-deficient mutant, we show here that expansion of the forespore membrane is severely inhibited in spo9Δ cells. Electron microscopy revealed significant accumulation membrane vesicles in spo9Δ cells. We suggest that lack of GGPS activity in a spo9 mutant results in impaired protein prenylation in certain proteins responsible for secretory function, thereby inhibiting forespore membrane formation.

scholarly journals Conversion from Archaeal Geranylgeranyl Diphosphate Synthase to Farnesyl Diphosphate Synthase

1997 ◽  
Vol 272 (8) ◽  
pp. 5192-5198 ◽  
Author(s):  
Shin-ichi Ohnuma ◽  
Kazutake Hirooka ◽  
Chikara Ohto ◽  
Tokuzo Nishino
Keyword(s):  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate

scholarly journals Characterization of Potential Drug Targets Farnesyl Diphosphate Synthase and Geranylgeranyl Diphosphate Synthase in Schistosoma mansoni

2013 ◽  
Vol 57 (12) ◽  
pp. 5969-5976 ◽  
Author(s):  
Peter D. Ziniel ◽  
Janish Desai ◽  
Cynthia L. Cass ◽  
Craig Gatto ◽  
Eric Oldfield ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Drug Targets ◽  
Protein Characterization ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Potential Drug ◽  
Geranylgeranyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate ◽  
Potential Drug Targets

ABSTRACTSchistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here thatSchistosoma mansonifarnesyl diphosphate synthase (SmFPPS) and geranylgeranyl diphosphate synthase (SmGGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinantSmFPPS andSmGGPPS for subsequent kinetic characterization and testing against a variety of bisphosphonate inhibitors. RecombinantSmFPPS was found to be a soluble 44.2-kDa protein, whileSmGGPPS was a soluble 38.3-kDa protein. Characterization of the substrate utilization of the two enzymes indicates that they have overlapping substrate specificities. AgainstSmFPPS, several bisphosphonates had 50% inhibitory concentrations (IC50s) in the low micromolar to nanomolar range; these inhibitors had significantly less activity againstSmGGPPS. Several lipophilic bisphosphonates were active againstex vivoadult worms, with worm death occurring over 4 to 6 days. These results indicate that FPPS and GGPPS could be of interest in the context of the emerging resistance to praziquantel in schistosomiasis therapy.

scholarly journals Farnesyl diphosphate synthase; regulation of product specificity.

2005 ◽  
Vol 52 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Anna Szkopińska ◽  
Danuta Płochocka
Keyword(s):  
Environmental Changes ◽  
Gene Families ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Type I ◽  
Isopentenyl Diphosphate ◽  
Product Specificity ◽  
Dimethylallyl Diphosphate ◽  
Key Enzyme ◽  
Synthase Regulation

Farnesyl diphosphate synthase (FPPS) is a key enzyme in isoprenoid biosynthesis which supplies sesquiterpene precursors for several classes of essential metabolites including sterols, dolichols, ubiquinones and carotenoids as well as substrates for farnesylation and geranylgeranylation of proteins. It catalyzes the sequential head-to-tail condensation of two molecules of isopentenyl diphosphate with dimethylallyl diphosphate. The enzyme is a homodimer of subunits, typically having two aspartate-rich motifs with two sets of substrate binding sites for an allylic diphosphate and isopentenyl diphosphate per homodimer. The synthase amino-acid residues at the 4th and 5th positions before the first aspartate rich motif mainly determine product specificity. Hypothetically, type I (eukaryotic) and type II (eubacterial) FPPSs evolved from archeal geranylgeranyl diphosphate synthase by substitutions in the chain length determination region. FPPS belongs to enzymes encoded by gene families. In plants this offers the possibility of differential regulation in response to environmental changes or to herbivore or pathogen attack.

scholarly journals Conversion from Farnesyl Diphosphate Synthase to Geranylgeranyl Diphosphate Synthase by Random Chemical Mutagenesis

1996 ◽  
Vol 271 (17) ◽  
pp. 10087-10095 ◽  
Author(s):  
Shin-ichi Ohnuma ◽  
Takeshi Nakazawa ◽  
Hisashi Hemmi ◽  
Anna-Maria Hallberg ◽  
Tanetoshi Koyama ◽  
...  
Keyword(s):  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Chemical Mutagenesis ◽  
Geranylgeranyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate
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