Genomes and Genes
Summary: Phosphoric or pyrophosphoric acid esters of polyisoprenoids.
- Vedula L, Zhao Y, Coates R, Koyama T, Cane D, Christianson D. Exploring biosynthetic diversity with trichodiene synthase. Arch Biochem Biophys. 2007;466:260-6 pubmed
- Faraldos J, Zhao Y, O Maille P, Noel J, Coates R. Interception of the enzymatic conversion of farnesyl diphosphate to 5-epi-aristolochene by using a fluoro substrate analogue: 1-fluorogermacrene A from (2E,6Z)-6-fluorofarnesyl diphosphate. Chembiochem. 2007;8:1826-33 pubmed
- Hsieh F, Chang T, Ko T, Wang A. Structure and mechanism of an Arabidopsis medium/long-chain-length prenyl pyrophosphate synthase. Plant Physiol. 2011;155:1079-90 pubmed publisher..Taken together, these results suggest that AtPPPS is endowed with a unique functionality among the known PTSs. ..
- Jin Y, Williams D, Croteau R, Coates R. Taxadiene synthase-catalyzed cyclization of 6-fluorogeranylgeranyl diphosphate to 7-fluoroverticillenes. J Am Chem Soc. 2005;127:7834-42 pubmed
- Shishova E, Di Costanzo L, Cane D, Christianson D. X-ray crystal structure of aristolochene synthase from Aspergillus terreus and evolution of templates for the cyclization of farnesyl diphosphate. Biochemistry. 2007;46:1941-51 pubmed..Across the greater family of terpenoid cyclases, this template is highly evolvable within a conserved alpha-helical fold for the synthesis of terpene natural products of diverse structure and stereochemistry. ..
- Takahashi S, Yeo Y, Greenhagen B, McMullin T, Song L, Maurina Brunker J, et al. Metabolic engineering of sesquiterpene metabolism in yeast. Biotechnol Bioeng. 2007;97:170-81 pubmed
- Christianson D. Structural biology and chemistry of the terpenoid cyclases. Chem Rev. 2006;106:3412-42 pubmed
- Prisic S, Xu J, Coates R, Peters R. Probing the role of the DXDD motif in Class II diterpene cyclases. Chembiochem. 2007;8:869-74 pubmed
- Schmidt A, Gershenzon J. Cloning and characterization of isoprenyl diphosphate synthases with farnesyl diphosphate and geranylgeranyl diphosphate synthase activity from Norway spruce (Picea abies) and their relation to induced oleoresin formation. Phytochemistry. 2007;68:2649-59 pubmed..Of the three genes, only PaIDS 5 displayed a significant increase in transcript level in response to methyl jasmonate spraying, suggesting its involvement in induced oleoresin biosynthesis. ..
- Tatar L, Marolda C, Polischuk A, van Leeuwen D, Valvano M. An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling. Microbiology. 2007;153:2518-29 pubmed..Together, the results support the notion that YbjG, and to a lesser extent YeiU, exert their enzymic activity on the periplasmic side of the plasma membrane and are implicated in the recycling of periplasmic Und-PP molecules. ..
- El Ghachi M, Derbise A, Bouhss A, Mengin Lecreulx D. Identification of multiple genes encoding membrane proteins with undecaprenyl pyrophosphate phosphatase (UppP) activity in Escherichia coli. J Biol Chem. 2005;280:18689-95 pubmed..coli and probably other bacterial species; they are the BacA enzyme and several members from a superfamily of phosphatases that, different from BacA, share in common a characteristic phosphatase sequence motif. ..
- Wei H, Fang L, Song J, Chatterjee S. Statin-inhibited endothelial permeability could be associated with its effect on PECAM-1 in endothelial cells. FEBS Lett. 2005;579:1272-8 pubmed..We speculate that lovastatin regulates PECAM-1 expression in HUVECs through the mevalonate-GGPP pathway by inhibiting of Rho small GTPase. ..
- Tsubaki M, Kato C, Nishinobo M, Ogaki M, Satou T, Ito T, et al. Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits macrophage inflammatory protein 1 alpha expression and secretion in mouse myeloma cells. Cancer Sci. 2008;99:152-8 pubmed..Accordingly, YM529/ONO-5920 appears to have promise for use in effective future therapy for osteolysis and myeloma cell growth that depends on MIP-1 alpha. ..
- Tong H, Holstein S, Hohl R. Simultaneous determination of farnesyl and geranylgeranyl pyrophosphate levels in cultured cells. Anal Biochem. 2005;336:51-9 pubmed..This method is suitable for the determination of the concentrations of FPP and GGPP in any cell type or tissue. ..
- Fujiwara K, Tsubaki M, Yamazoe Y, Nishiura S, Kawaguchi T, Ogaki M, et al. [Fluvastatin induces apoptosis on human tongue carcinoma cell line HSC-3]. Yakugaku Zasshi. 2008;128:153-8 pubmed..The results of this study also indicate that fluvastatin may be used as an anticancer agent for tongue carcinoma. ..
- Morofuji Y, Nakagawa S, So G, Hiu T, Horai S, Hayashi K, et al. Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol. 2010;30:727-35 pubmed publisher..The BBB-stabilizing effect of pitavastatin may be mediated partly through inhibition of the mevalonate pathway and subsequent up-regulation of claudin-5 expression...
- Bang S, Yoo S, Yang T, Cho H, Hwang S. Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3. J Biol Chem. 2010;285:19362-71 pubmed publisher..Our results may provide useful chemical information to elucidate TRPV3 physiology and novel pain-related metabolisms. ..
- Zhao T, Le Francois B, Goss G, Ding K, Bradbury P, Dimitroulakos J. Lovastatin inhibits EGFR dimerization and AKT activation in squamous cell carcinoma cells: potential regulation by targeting rho proteins. Oncogene. 2010;29:4682-92 pubmed publisher..In BR21, patients showed a trend for improvement in OS (HR: 0.69, P=0.098) and DSS (HR: 0.62, P=0.048), but there was no statin x treatment interaction effect (P=0.34 and P=0.51 for OS and DSS, respectively)...
- Nonaka M, Uota S, Saitoh Y, Takahashi M, Sugimoto H, Amet T, et al. Role for protein geranylgeranylation in adult T-cell leukemia cell survival. Exp Cell Res. 2009;315:141-50 pubmed publisher..These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL. ..
- Oh D, Yoon J, Moon M, Hwang J, Choe H, Lee J, et al. Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92. J Biol Chem. 2008;283:21054-64 pubmed publisher..FPP and NAG increased intracellular Ca(2+) levels in cultured DRG neurons. These results suggest that FPP and NAG play a role in the sensory nervous system through activation of GPR92. ..
- Kinjoh T, Kaneko Y, Itoyama K, Mita K, Hiruma K, Shinoda T. Control of juvenile hormone biosynthesis in Bombyx mori: cloning of the enzymes in the mevalonate pathway and assessment of their developmental expression in the corpora allata. Insect Biochem Mol Biol. 2007;37:808-18 pubmed..Altogether, our results point to a relationship between JH biosynthesis and expression of most JH biosynthetic enzymes in the CA. ..
- Guo R, Cao R, Liang P, Ko T, Chang T, Hudock M, et al. Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases. Proc Natl Acad Sci U S A. 2007;104:10022-7 pubmed
- Shishova E, Yu F, Miller D, Faraldos J, Zhao Y, Coates R, et al. X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis. J Biol Chem. 2008;283:15431-9 pubmed publisher..Taken together, these structures provide 12 independent "snapshots" of substrate or product complexes that suggest a possible sequence for metal ion binding and conformational changes required for catalysis. ..
- Prisic S, Peters R. Synergistic substrate inhibition of ent-copalyl diphosphate synthase: a potential feed-forward inhibition mechanism limiting gibberellin metabolism. Plant Physiol. 2007;144:445-54 pubmed..Finally, the observed synergistic substrate/feed-forward inhibition of CPS also seems to provide a novel example of direct regulation of enzymatic activity in hormone biosynthesis. ..
- Green S, Friel E, Matich A, Beuning L, Cooney J, Rowan D, et al. Unusual features of a recombinant apple alpha-farnesene synthase. Phytochemistry. 2007;68:176-88 pubmed publisher..This is the first demonstration of a sesquiterpene synthase possessing prenyltransferase activity...
- Asadollahi M, Maury J, Schalk M, Clark A, Nielsen J. Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae. Biotechnol Bioeng. 2010;106:86-96 pubmed publisher..This could be explained by a toxicity effect of cubebol, possibly resulting in higher transcription levels for the genes under control of MET3 promoter, which could lead to accumulation of squalene and ergosterol. ..
- Lee S, Kim Y, Song S, Kim Y. Stabilization and translocation of p53 to mitochondria is linked to Bax translocation to mitochondria in simvastatin-induced apoptosis. Biochem Biophys Res Commun. 2010;391:1592-7 pubmed publisher..Taken together, these all indicate that stabilization and translocation of p53 to mitochondria is involved in Bax translocation to mitochondria in simvastatin-induced apoptosis. ..
- Mikusova K, Huang H, Yagi T, Holsters M, Vereecke D, D Haeze W, et al. Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose. J Bacteriol. 2005;187:8020-5 pubmed..Together, these proteins (Rv3790 and Rv3791) are able to catalyze the epimerization, although neither protein individually is sufficient to support the activity. ..
- Cordle A, Landreth G. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses. J Neurosci. 2005;25:299-307 pubmed..We argue that the statin-mediated decrease in AD risk arises from their pleiotropic actions, effecting a reduction in neuronal Abeta production and microglia-directed inflammation. ..
- Levy B, Hickey L, Morris A, Larvie M, Keledjian R, Petasis N, et al. Novel polyisoprenyl phosphates block phospholipase D and human neutrophil activation in vitro and murine peritoneal inflammation in vivo. Br J Pharmacol. 2005;146:344-51 pubmed..b>Polyisoprenyl phosphates (PIPPs) are constituents of human leukocyte membranes that regulate pivotal intracellular enzymes, such ..
- Thulasiram H, Poulter C. Farnesyl diphosphate synthase: the art of compromise between substrate selectivity and stereoselectivity. J Am Chem Soc. 2006;128:15819-23 pubmed
- Tong H, Wiemer A, Neighbors J, Hohl R. Quantitative determination of farnesyl and geranylgeranyl diphosphate levels in mammalian tissue. Anal Biochem. 2008;378:138-43 pubmed publisher..This method allows for determination of FPP and GGPP concentrations in any tissue type and is sensitive enough to detect changes following treatment with inhibitors of isoprenoid biosynthesis. ..
- Tsubaki M, Yamazoe Y, Yanae M, Satou T, Itoh T, Kaneko J, et al. Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-? as angiogenic factors in mouse osteosarcoma. Cytokine. 2011;54:100-7 pubmed publisher..These results suggest that statins are potentially useful as anti-angiogenic agents for the treatment of osteosarcoma. ..
- Paradise E, Kirby J, Chan R, Keasling J. Redirection of flux through the FPP branch-point in Saccharomyces cerevisiae by down-regulating squalene synthase. Biotechnol Bioeng. 2008;100:371-8 pubmed publisher..The levels of these three metabolites were dependent not only upon the level of ERG9 repression, but also the timing of its repression relative to the induction of ADS and genes responsible for enhancing flux to FPP. ..
- Argmann C, Edwards J, Sawyez C, O Neil C, Hegele R, Pickering J, et al. Regulation of macrophage cholesterol efflux through hydroxymethylglutaryl-CoA reductase inhibition: a role for RhoA in ABCA1-mediated cholesterol efflux. J Biol Chem. 2005;280:22212-21 pubmed..Finally, statin treatment inhibited cholesteryl ester accumulation in macrophages challenged with atherogenic hypertriglyceridemic very low density lipoproteins indicating that statins can regulate foam cell formation...
- Bernard R, El Ghachi M, Mengin Lecreulx D, Chippaux M, Denizot F. BcrC from Bacillus subtilis acts as an undecaprenyl pyrophosphate phosphatase in bacitracin resistance. J Biol Chem. 2005;280:28852-7 pubmed..coli, a member of the PF02673 family of the Protein family (Pfam) database. Thus, BcrC(Bs) and its orthologs form a new class of proteins within the PAP2 phosphatase superfamily, and likely all of them share a UPP phosphatase activity...
- Miller D, Yu F, Allemann R. Aristolochene synthase-catalyzed cyclization of 2-fluorofarnesyl-diphosphate to 2-fluorogermacrene A. Chembiochem. 2007;8:1819-25 pubmed
- Fujimoto M, Oka T, Murata T, Hori M, Ozaki H. Fluvastatin inhibits mast cell degranulation without changing the cytoplasmic Ca2+ level. Eur J Pharmacol. 2009;602:432-8 pubmed publisher..The statin-induced inhibitory action may be mediated by the suppression of geranylgeranyl transferase via the depletion of intracellular mevalonic acid. ..
- Murthy S, Tong H, Hohl R. Regulation of fatty acid synthesis by farnesyl pyrophosphate. J Biol Chem. 2005;280:41793-804 pubmed..FPP prevented the increase in FAS mRNA in mevalonate-depleted cells without altering SREBP-2 activation. Thus, FPP regulates fatty acid synthesis by a mechanism that is likely independent of the SREBP pathway. ..
- Harris L, Saparno A, Johnston A, Prisic S, Xu M, Allard S, et al. The maize An2 gene is induced by Fusarium attack and encodes an ent-copalyl diphosphate synthase. Plant Mol Biol. 2005;59:881-94 pubmed publisher..However, it is not known whether An2 is involved in defense-related secondary metabolism in addition to GA synthesis...
- Lane K, Beese L. Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res. 2006;47:681-99 pubmed..Such complexes may assist in the design of inhibitors that could lead to treatments for cancer, viral infection, and a number of deadly parasitic diseases. ..
- Song L. A soluble form of phosphatase in Saccharomyces cerevisiae capable of converting farnesyl diphosphate into E,E-farnesol. Appl Biochem Biotechnol. 2006;128:149-58 pubmed..0 and 8.5, hydrolysis of GPP was observed only at pH 7.0. Mg2+ and Mn2+ inhibited hydrolysis of FPP and GGPP, and GGPP was more sensitive to Mg2+ inhibition than FPP. The rate of FPP hydrolysis increased in the presence of Triton X-100...
- Kloer D, Welsch R, Beyer P, Schulz G. Structure and reaction geometry of geranylgeranyl diphosphate synthase from Sinapis alba. Biochemistry. 2006;45:15197-204 pubmed
- Kobayashi K, Suzuki M, Tang J, Nagata N, Ohyama K, Seki H, et al. Lovastatin insensitive 1, a Novel pentatricopeptide repeat protein, is a potential regulatory factor of isoprenoid biosynthesis in Arabidopsis. Plant Cell Physiol. 2007;48:322-31 pubmed..Our investigation revealed that the post-transcriptional regulation of mitochondrial RNA may be involved in isoprenoid biosynthesis in both the MVA and MEP pathways. ..
- Ling Y, Li Z, Miranda K, Oldfield E, Moreno S. The farnesyl-diphosphate/geranylgeranyl-diphosphate synthase of Toxoplasma gondii is a bifunctional enzyme and a molecular target of bisphosphonates. J Biol Chem. 2007;282:30804-16 pubmed
- Kotamraju S, Williams C, Willams C, Kalyanaraman B. Statin-induced breast cancer cell death: role of inducible nitric oxide and arginase-dependent pathways. Cancer Res. 2007;67:7386-94 pubmed..NO biosynthesis by NOS. We conclude that iNOS-mediated (.)NO is responsible in part for the proapoptotic, tumoricidal, and antiproliferative effects of statins in MCF-7 cells. ..
- Guo R, Ko T, Chen A, Kuo C, Wang A, Liang P. Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis. J Biol Chem. 2005;280:20762-74 pubmed..Other conserved residues, including His(43), Ser(71), Asn(74), and Arg(77), may serve as general acid/base and pyrophosphate carrier. Our results here improve the understanding of the UPPs enzyme reaction significantly. ..
- Kato J, Fujisaki S, Nakajima K, Nishimura Y, Sato M, Nakano A. The Escherichia coli homologue of yeast RER2, a key enzyme of dolichol synthesis, is essential for carrier lipid formation in bacterial cell wall synthesis. J Bacteriol. 1999;181:2733-8 pubmed
- Peters R, Ravn M, Coates R, Croteau R. Bifunctional abietadiene synthase: free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites. J Am Chem Soc. 2001;123:8974-8 pubmed..In addition, both mutant enzymes enhance the activity of wild-type abietadiene synthase with geranylgeranyl diphosphate as substrate. The implications of these results for the kinetic mechanism of abietadiene synthase are discussed. ..
- Campos N, Rodríguez Concepción M, Sauret Güeto S, Gallego F, Lois L, Boronat A. Escherichia coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from mevalonate: a novel system for the genetic analysis of the 2-C-methyl-d-erythritol 4-phosphate pathway for isoprenoid biosynthesis. Biochem J. 2001;353:59-67 pubmed..We used this system to show that the ygbP, ychB and ygbB genes are essential in E. coli and that the steps catalysed by the products of these genes belong to the trunk line of the MEP pathway...
- Saisho Y, Morimoto A, Umeda T. Determination of farnesyl pyrophosphate in dog and human plasma by high-performance liquid chromatography with fluorescence detection. Anal Biochem. 1997;252:89-95 pubmed..2 and 6.6 ng/ml, respectively. The method was utilized to examine the circadian rhythm of FPP in dog plasma, and different rhythms were observed between feeding and fasting dogs. ..
- Lesburg C, Zhai G, Cane D, Christianson D. Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology. Science. 1997;277:1820-4 pubmed
- Oulmouden A, Karst F. Nucleotide sequence of the ERG12 gene of Saccharomyces cerevisiae encoding mevalonate kinase. Curr Genet. 1991;19:9-14 pubmed..In addition, we show that mevalonate kinase is not a rate-limiting enzyme; however its sensitivity to FFP could be a key regulatory mechanism in the sterol pathway of yeast. ..
- Chang S, Chen Y, Wang A, Liang P. Identification of the active conformation and the importance of length of the flexible loop 72-83 in regulating the conformational change of undecaprenyl pyrophosphate synthase. Biochemistry. 2003;42:14452-9 pubmed..We conclude that the closed conformation is apparently the active conformation. Change of the length of the loop 72-83 impairs the ability of conformational change and causes remarkably lower activity of UPPs. ..
- Tafazoli F, Magnusson K, Zheng L. Disruption of epithelial barrier integrity by Salmonella enterica serovar typhimurium requires geranylgeranylated proteins. Infect Immun. 2003;71:872-81 pubmed..These results suggest that activation of geranylgeranylated proteins, including Rac1 and Cdc42, is critical for disruption of barrier integrity by serovar Typhimurium in polarized MDCK-1 cells. ..
- Peters R, Croteau R. Abietadiene synthase catalysis: conserved residues involved in protonation-initiated cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate. Biochemistry. 2002;41:1836-42 pubmed..A functional role was also suggested for the cryptic insertional element found in abietadiene synthase and other diterpene synthases that carry out similar protonation-initiated cyclizations. ..
- Schepmann H, Pang J, Matsuda S. Cloning and characterization of Ginkgo biloba levopimaradiene synthase which catalyzes the first committed step in ginkgolide biosynthesis. Arch Biochem Biophys. 2001;392:263-9 pubmed..This is the first cloned ginkgolide biosynthetic gene and the first in vitro observation of an isolated ginkgolide biosynthetic enzyme. ..
- Pan J, Chiou S, Liang P. Product distribution and pre-steady-state kinetic analysis of Escherichia coli undecaprenyl pyrophosphate synthase reaction. Biochemistry. 2000;39:10936-42 pubmed..001 s(-1) might govern the UPPs reaction rate under the steady-state condition in the absence of Triton. ..