polyisoprenyl phosphates

Summary

Summary: Phosphoric or pyrophosphoric acid esters of polyisoprenoids.

Top Publications

  1. ncbi Structural biology and chemistry of the terpenoid cyclases
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    Chem Rev 106:3412-42. 2006
  2. ncbi Stabilization and translocation of p53 to mitochondria is linked to Bax translocation to mitochondria in simvastatin-induced apoptosis
    Sang Kyu Lee
    Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305 764, Republic of Korea
    Biochem Biophys Res Commun 391:1592-7. 2010
  3. pmc Metabolic engineering of sesquiterpene metabolism in yeast
    Shunji Takahashi
    Department of Plant and Soil Sciences, University of Kentucky, Lexington, Kentucky 40546 0312, USA
    Biotechnol Bioeng 97:170-81. 2007
  4. ncbi Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells
    Zhihong Jiang
    Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 89:168-78. 2004
  5. pmc The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis
    T P Sun
    Department of Botany, Duke University, Durham, North Carolina 27708 1000
    Plant Cell 6:1509-18. 1994
  6. ncbi Statin-induced breast cancer cell death: role of inducible nitric oxide and arginase-dependent pathways
    Srigiridhar Kotamraju
    Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Cancer Res 67:7386-94. 2007
  7. ncbi The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity
    Meriem El Ghachi
    Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moleculaire et Cellulaire, UMR 8619 CNRS, Universite Paris Sud, Batiment 430, 91405 Orsay, France
    J Biol Chem 279:30106-13. 2004
  8. ncbi 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses
    Andrew Cordle
    Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Neurosci 25:299-307. 2005
  9. ncbi An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling
    Laura D Tatar
    Department of Microbiology and Immunology, Infectious Diseases Research Group, Siebens Drake Research Institute, University of Western Ontario, London, Ontario N6A 5C1, Canada
    Microbiology 153:2518-29. 2007
  10. ncbi Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase
    A Montalvetti
    Laboratory of Molecular Parasitology, Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA
    J Biol Chem 276:33930-7. 2001

Detail Information

Publications192 found, 100 shown here

  1. ncbi Structural biology and chemistry of the terpenoid cyclases
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    Chem Rev 106:3412-42. 2006
  2. ncbi Stabilization and translocation of p53 to mitochondria is linked to Bax translocation to mitochondria in simvastatin-induced apoptosis
    Sang Kyu Lee
    Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305 764, Republic of Korea
    Biochem Biophys Res Commun 391:1592-7. 2010
    ..Taken together, these all indicate that stabilization and translocation of p53 to mitochondria is involved in Bax translocation to mitochondria in simvastatin-induced apoptosis...
  3. pmc Metabolic engineering of sesquiterpene metabolism in yeast
    Shunji Takahashi
    Department of Plant and Soil Sciences, University of Kentucky, Lexington, Kentucky 40546 0312, USA
    Biotechnol Bioeng 97:170-81. 2007
    ....
  4. ncbi Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells
    Zhihong Jiang
    Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 89:168-78. 2004
    ..Further elucidation of the mechanisms of lovastatin-induced up-regulation of Bim and apoptosis in glioblastoma cells are important in determining a potential role for lovastatin as a chemotherapy agent...
  5. pmc The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis
    T P Sun
    Department of Botany, Duke University, Durham, North Carolina 27708 1000
    Plant Cell 6:1509-18. 1994
    ..Subcellular localization of the GA1 protein was studied using 35S-labeled GA1 protein and isolated pea chloroplasts. The results showed that the GA1 protein is imported into and processed in pea chloroplasts in vitro...
  6. ncbi Statin-induced breast cancer cell death: role of inducible nitric oxide and arginase-dependent pathways
    Srigiridhar Kotamraju
    Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Cancer Res 67:7386-94. 2007
    ..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...
  7. ncbi The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity
    Meriem El Ghachi
    Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moleculaire et Cellulaire, UMR 8619 CNRS, Universite Paris Sud, Batiment 430, 91405 Orsay, France
    J Biol Chem 279:30106-13. 2004
    ..This is the first gene encoding undecaprenyl pyrophosphate phosphatase identified to date. Considering its newly identified function, we propose to rename the bacA gene uppP...
  8. ncbi 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses
    Andrew Cordle
    Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Neurosci 25:299-307. 2005
    ..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...
  9. ncbi An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling
    Laura D Tatar
    Department of Microbiology and Immunology, Infectious Diseases Research Group, Siebens Drake Research Institute, University of Western Ontario, London, Ontario N6A 5C1, Canada
    Microbiology 153:2518-29. 2007
    ..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...
  10. ncbi Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase
    A Montalvetti
    Laboratory of Molecular Parasitology, Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA
    J Biol Chem 276:33930-7. 2001
    ..The protein contains a unique 11-mer insertion located near the active site, together with other sequence differences that may facilitate the development of novel anti-Chagasic agents...
  11. ncbi Regulation of macrophage cholesterol efflux through hydroxymethylglutaryl-CoA reductase inhibition: a role for RhoA in ABCA1-mediated cholesterol efflux
    Carmen A Argmann
    Robarts Research Institute, Vascular Biology Group, and the Departments of Medicine and Biochemistry, The University of Western Ontario, London, Ontario N6A 5K8, Canada
    J Biol Chem 280:22212-21. 2005
    ..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...
  12. ncbi Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukemia cells to lovastatin-induced apoptosis
    Jianghong Wu
    Department of Cellular and Molecular Biology, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
    Cancer Res 64:6461-8. 2004
    ..Our study suggests that lovastatin, alone or in combination with a MEK1 inhibitor, may represent a new and immediately available therapeutic approach to combat tumors with activated ERK1/2, such as AML...
  13. pmc A bifunctional geranyl and geranylgeranyl diphosphate synthase is involved in terpene oleoresin formation in Picea abies
    Axel Schmidt
    Max Planck Institute for Chemical Ecology, Department of Biochemistry, Beutenberg Campus, D 07745 Jena, Germany
    Plant Physiol 152:639-55. 2010
    ....
  14. ncbi Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae
    Mohammad A Asadollahi
    Department of Systems Biology, Center for Microbial Biotechnology, Building 223, Technical University of Denmark DTU, DK 2800 Kgs Lyngby, Denmark
    Biotechnol Bioeng 106:86-96. 2010
    ..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...
  15. pmc Disruption of epithelial barrier integrity by Salmonella enterica serovar typhimurium requires geranylgeranylated proteins
    Farideh Tafazoli
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Linkoping University, Sweden
    Infect Immun 71:872-81. 2003
    ..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...
  16. pmc Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics
    Manuel Rodriguez-Concepcion
    Departament de Bioquimica i Biologia Molecular, Facultat de Quimica, Universitat de Barcelona, Martí i Franquès 1 7, 08028 Barcelona, Spain
    Plant Physiol 130:1079-89. 2002
  17. pmc An insect farnesyl phosphatase homologous to the N-terminal domain of soluble epoxide hydrolase
    Li Cao
    Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA
    Biochem Biophys Res Commun 380:188-92. 2009
    ..4muM. Thus, our data identify Phos15739 as a FPP phosphatase that likely catalyzes the hydrolysis of FPP to farnesol in D. melanogaster...
  18. ncbi Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells
    Yoichi Morofuji
    Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, 1 7 1 Sakamoto, Nagasaki 852 8501, Japan
    Cell Mol Neurobiol 30:727-35. 2010
    ..The BBB-stabilizing effect of pitavastatin may be mediated partly through inhibition of the mevalonate pathway and subsequent up-regulation of claudin-5 expression...
  19. pmc X-ray crystal structure of aristolochene synthase from Aspergillus terreus and evolution of templates for the cyclization of farnesyl diphosphate
    Ekaterina Y Shishova
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 46:1941-51. 2007
    ..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...
  20. ncbi Chain elongation in the isoprenoid biosynthetic pathway
    B A Kellogg
    Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA
    Curr Opin Chem Biol 1:570-8. 1997
    ....
  21. ncbi Inhibition of geranylgeranylation mediates the effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors on microglia
    Xiaoning Bi
    Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA 92617 1695, USA
    J Biol Chem 279:48238-45. 2004
    ....
  22. pmc Spider mite-induced (3S)-(E)-nerolidol synthase activity in cucumber and lima bean. The first dedicated step in acyclic C11-homoterpene biosynthesis
    H J Bouwmeester
    Research Institute for Agrobiology and Soil Fertility, P O Box 14, 6700 AA Wageningen, The Netherlands
    Plant Physiol 121:173-80. 1999
    ..Thus, (3S)-(E)-nerolidol synthase is a good candidate for a regulatory role in the release of the important signaling molecule 4,8-dimethyl-1,3(E),7-nonatriene...
  23. pmc Regulation of product chain length by isoprenyl diphosphate synthases
    L C Tarshis
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 93:15018-23. 1996
    ..A model was constructed to show how the growth of a long chain prenyl product may proceed by creation of a hydrophobic passageway from the FPS active site to the outside surface of the enzyme...
  24. ncbi Lovastatin inhibits EGFR dimerization and AKT activation in squamous cell carcinoma cells: potential regulation by targeting rho proteins
    T T Zhao
    Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    Oncogene 29:4682-92. 2010
    ..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)...
  25. ncbi Statin-inhibited endothelial permeability could be associated with its effect on PECAM-1 in endothelial cells
    Heming Wei
    Laboratory of Atherosclerosis and Vascular Biology, Johns Hopkins Singapore National Heart Centre Vascular Biology Program, 31 Biopolis Way, 03 00 The Nanos Building, Singapore 138669, Singapore
    FEBS Lett 579:1272-8. 2005
    ..We speculate that lovastatin regulates PECAM-1 expression in HUVECs through the mevalonate-GGPP pathway by inhibiting of Rho small GTPase...
  26. ncbi Unusual features of a recombinant apple alpha-farnesene synthase
    Sol Green
    HortResearch, Mt Albert Research Centre, Horticultural and Food Research Institute of New Zealand, Private Bag 92169, Auckland, New Zealand
    Phytochemistry 68:176-88. 2007
    ..This is the first demonstration of a sesquiterpene synthase possessing prenyltransferase activity...
  27. pmc Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose
    Katarina Mikusova
    Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia
    J Bacteriol 187:8020-5. 2005
    ..Together, these proteins (Rv3790 and Rv3791) are able to catalyze the epimerization, although neither protein individually is sufficient to support the activity...
  28. pmc Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3
    Sangsu Bang
    Korea University Graduate School of Medicine, Seoul 136 705, Korea
    J Biol Chem 285:19362-71. 2010
    ..Taken together, our data suggest that FPP is the firstly identified endogenous TRPV3 activator that causes nociception. Our results may provide useful chemical information to elucidate TRPV3 physiology and novel pain-related metabolisms...
  29. ncbi Quantitative determination of farnesyl and geranylgeranyl diphosphate levels in mammalian tissue
    Huaxiang Tong
    Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    Anal Biochem 378:138-43. 2008
    ..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...
  30. ncbi Redirection of flux through the FPP branch-point in Saccharomyces cerevisiae by down-regulating squalene synthase
    Eric M Paradise
    Department of Chemical Engineering, University of California, Berkeley, California 94720, USA
    Biotechnol Bioeng 100:371-8. 2008
    ..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...
  31. ncbi The LPP1 and DPP1 gene products account for most of the isoprenoid phosphate phosphatase activities in Saccharomyces cerevisiae
    A Faulkner
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 274:14831-7. 1999
    ....
  32. ncbi Simultaneous determination of farnesyl and geranylgeranyl pyrophosphate levels in cultured cells
    Huaxiang Tong
    Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    Anal Biochem 336:51-9. 2005
    ..This method is suitable for the determination of the concentrations of FPP and GGPP in any cell type or tissue...
  33. pmc Farnesyl diphosphate synthase: the art of compromise between substrate selectivity and stereoselectivity
    Hirekodathakallu V Thulasiram
    Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, USA
    J Am Chem Soc 128:15819-23. 2006
    ....
  34. ncbi Regulation of fatty acid synthesis by farnesyl pyrophosphate
    Shubha Murthy
    Department of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 280:41793-804. 2005
    ..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...
  35. ncbi A role of the amino acid residue located on the fifth position before the first aspartate-rich motif of farnesyl diphosphate synthase on determination of the final product
    S i Ohnuma
    Department of Biochemistry and Engineering, Tohoku University, Aoba Aramaki, Aoba ku, Sendai 980 77 Japan
    J Biol Chem 271:30748-54. 1996
    ..This interaction must prevent further condensation of isopentenyl diphosphate...
  36. ncbi The farnesyl-diphosphate/geranylgeranyl-diphosphate synthase of Toxoplasma gondii is a bifunctional enzyme and a molecular target of bisphosphonates
    Yan Ling
    Department of Pathobiology, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    J Biol Chem 282:30804-16. 2007
    ....
  37. pmc Structure and mechanism of an Arabidopsis medium/long-chain-length prenyl pyrophosphate synthase
    Fu Lien Hsieh
    Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan
    Plant Physiol 155:1079-90. 2011
    ..Taken together, these results suggest that AtPPPS is endowed with a unique functionality among the known PTSs...
  38. ncbi Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits macrophage inflammatory protein 1 alpha expression and secretion in mouse myeloma cells
    Masanobu Tsubaki
    Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi Osaka 577 8502, Japan
    Cancer Sci 99:152-8. 2008
    ..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...
  39. ncbi 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
    Axel Schmidt
    Max Planck Institute for Chemical Ecology, Department of Biochemistry, Hans Knöll Str 8, D 07745 Jena, Germany
    Phytochemistry 68:2649-59. 2007
    ..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...
  40. pmc Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers
    Fernando Lopez-Gallego
    Department of Biochemistry, University of Minnesota, Paul, MN 55108, USA
    Chembiochem 11:1093-106. 2010
    ..Structural modeling suggests that differences in the active site and the loop that covers the active site of the two enzymes might explain their different catalytic fidelities...
  41. ncbi 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
    Sing Yang Chang
    Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan
    Biochemistry 42:14452-9. 2003
    ..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...
  42. pmc Isoprenoids as mediators of the biological effects of statins
    James K Liao
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02139, USA
    J Clin Invest 110:285-8. 2002
  43. ncbi Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-β as angiogenic factors in mouse osteosarcoma
    Masanobu Tsubaki
    Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi Osaka, Japan
    Cytokine 54:100-7. 2011
    ..These results suggest that statins are potentially useful as anti-angiogenic agents for the treatment of osteosarcoma...
  44. ncbi 3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture
    C Guijarro
    Instituto de Investigacion Medica, Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Spain
    Circ Res 83:490-500. 1998
    ..The present data suggest that interference with protein prenylation by HMG-CoA reductase inhibitors or other agents may provide new strategies for the prevention of neointimal thickening...
  45. ncbi Determination of farnesyl pyrophosphate in dog and human plasma by high-performance liquid chromatography with fluorescence detection
    Y Saisho
    Shionogi Research Laboratories, Shionogi and Co, Ltd, Osaka, Japan
    Anal Biochem 252:89-95. 1997
    ..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...
  46. ncbi Fluvastatin inhibits mast cell degranulation without changing the cytoplasmic Ca2+ level
    Masanori Fujimoto
    Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan
    Eur J Pharmacol 602:432-8. 2009
    ..The statin-induced inhibitory action may be mediated by the suppression of geranylgeranyl transferase via the depletion of intracellular mevalonic acid...
  47. ncbi Role for protein geranylgeranylation in adult T-cell leukemia cell survival
    Mizuho Nonaka
    Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1 5 45 Bunkyo Ku, Tokyo 113 8510, Japan
    Exp Cell Res 315:141-50. 2009
    ..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...
  48. ncbi Design and structure-activity relationships of potent and selective inhibitors of undecaprenyl pyrophosphate synthase (UPPS): tetramic, tetronic acids and dihydropyridin-2-ones
    Stefan Peukert
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 18:1840-4. 2008
    ..Synthesis and structure-activity relationship patterns for this class of compounds are discussed. Selectivity data and antibacterial activities for selected compounds are provided...
  49. ncbi Partial purification and characterization of the short-chain prenyltransferases, gernayl diphospate synthase and farnesyl diphosphate synthase, from Abies grandis (grand fir)
    D Tholl
    Max-Planck Institute of Chemical Ecology, Jena, Germany
    Arch Biochem Biophys 386:233-42. 2001
    ..The properties of both enzymes are broadly similar to those of other prenyltransferases. The apparent native molecular masses are 54 +/- 3 kDa for GPP synthase and 110 +/- 6 kDa fo..
  50. ncbi [Fluvastatin induces apoptosis on human tongue carcinoma cell line HSC-3]
    Kimiko Fujiwara
    Department of Pharmacy, Kinki University Hospital, Osakasayama City, Japan
    Yakugaku Zasshi 128:153-8. 2008
    ..The results of this study also indicate that fluvastatin may be used as an anticancer agent for tongue carcinoma...
  51. pmc X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis
    Ekaterina Y Shishova
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Biol Chem 283:15431-9. 2008
    ..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...
  52. ncbi Identification of multiple genes encoding membrane proteins with undecaprenyl pyrophosphate phosphatase (UppP) activity in Escherichia coli
    Meriem El Ghachi
    Laboratoire des Enveloppes Bactériennes et Antibiotiques, Unite Mixte de Recherche 8619 CNRS, Universite Paris Sud, 91405 Orsay, France
    J Biol Chem 280:18689-95. 2005
    ..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...
  53. pmc Synthesis, properties, and applications of diazotrifluropropanoyl-containing photoactive analogs of farnesyl diphosphate containing modified linkages for enhanced stability
    Marisa L Hovlid
    Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
    Chem Biol Drug Des 75:51-67. 2010
    ..coli extract was observed, suggesting that [32P]4 manifests significant selectivity and should hence be useful for identifying novel FPP-utilizing enzymes in crude protein preparations...
  54. ncbi Mevastatin induces apoptosis in HL60 cells dependently on decrease in phosphorylated ERK
    Shozo Nishida
    School of Pharmaceutical Sciences, Kinki University, Higashi Osaka, Japan
    Mol Cell Biochem 269:109-14. 2005
    ..The results of this study also suggested that mevastatin could be used as an anticancer agent...
  55. pmc Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92
    Da Young Oh
    Laboratory of G Protein Coupled Receptors and Department of Physiology, Korea University College of Medicine, Seoul, Korea
    J Biol Chem 283:21054-64. 2008
    ..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...
  56. ncbi Aristolochene synthase-catalyzed cyclization of 2-fluorofarnesyl-diphosphate to 2-fluorogermacrene A
    David J Miller
    School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff, CF10 3AT, UK
    Chembiochem 8:1819-25. 2007
    ....
  57. ncbi Structure and reaction geometry of geranylgeranyl diphosphate synthase from Sinapis alba
    Daniel P Kloer
    Institut fur Organische Chemie und Biochemie, Albert Ludwigs Universitat, Albertstrasse 21, D 79104 Freiburg im Breisgau, Germany
    Biochemistry 45:15197-204. 2006
    ....
  58. ncbi Lovastatin insensitive 1, a Novel pentatricopeptide repeat protein, is a potential regulatory factor of isoprenoid biosynthesis in Arabidopsis
    Keiko Kobayashi
    RIKEN Plant Science Center, 1 7 22, Suehirocho, Tsurumi ku, Yokohama, Japan
    Plant Cell Physiol 48:322-31. 2007
    ..Our investigation revealed that the post-transcriptional regulation of mitochondrial RNA may be involved in isoprenoid biosynthesis in both the MVA and MEP pathways...
  59. ncbi A soluble form of phosphatase in Saccharomyces cerevisiae capable of converting farnesyl diphosphate into E,E-farnesol
    Linsheng Song
    Bio Technical Resources, 1035 South 7th Street, Manitowoc, WI 54220, USA
    Appl Biochem Biotechnol 128:149-58. 2006
    ..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...
  60. ncbi Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I
    Kimberly T Lane
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Lipid Res 47:681-99. 2006
    ..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...
  61. ncbi The maize An2 gene is induced by Fusarium attack and encodes an ent-copalyl diphosphate synthase
    L J Harris
    Eastern Cereal and Oilseed Research Centre, Agriculture and Agri Food Canada, Building 21, Central Experimental Farm, K1A 0C6, Ottawa, Ont, Canada
    Plant Mol Biol 59:881-94. 2005
    ..However, it is not known whether An2 is involved in defense-related secondary metabolism in addition to GA synthesis...
  62. pmc Synergistic substrate inhibition of ent-copalyl diphosphate synthase: a potential feed-forward inhibition mechanism limiting gibberellin metabolism
    Sladjana Prisic
    Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011, USA
    Plant Physiol 144:445-54. 2007
    ..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...
  63. ncbi Probing the role of the DXDD motif in Class II diterpene cyclases
    Sladjana Prisic
    Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Molecular Biology Building, Ames, IA 50011, USA
    Chembiochem 8:869-74. 2007
  64. pmc Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases
    Rey Ting Guo
    Taiwan International Graduate Program, Institute of Biological Chemistry, Core Facility for Protein Crystallography, Academia Sinica, Taipei 115, Taiwan
    Proc Natl Acad Sci U S A 104:10022-7. 2007
    ....
  65. ncbi BcrC from Bacillus subtilis acts as an undecaprenyl pyrophosphate phosphatase in bacitracin resistance
    Remi Bernard
    Laboratoire de Chimie Bacterienne, Institut de Biologie Structurale et Microbiologie, Batiment 430, 91405 Orsay Cedex, France
    J Biol Chem 280:28852-7. 2005
    ..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...
  66. ncbi Taxadiene synthase-catalyzed cyclization of 6-fluorogeranylgeranyl diphosphate to 7-fluoroverticillenes
    Yinghua Jin
    Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    J Am Chem Soc 127:7834-42. 2005
    ....
  67. ncbi Amorpha-4,11-diene synthase: mechanism and stereochemistry of the enzymatic cyclization of farnesyl diphosphate
    Sarah Picaud
    Department of Chemistry and Biomedical Science, University of Kalmar, SE 39182 Kalmar, Sweden
    Arch Biochem Biophys 448:150-5. 2006
    ....
  68. ncbi Bifunctional abietadiene synthase: free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites
    R J Peters
    Institute of Biological Chemistry, Washington State University, Pullman, WA 99164-6340, USA
    J Am Chem Soc 123:8974-8. 2001
    ..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...
  69. ncbi Identification of a short (C15) chain Z-isoprenyl diphosphate synthase and a homologous long (C50) chain isoprenyl diphosphate synthase in Mycobacterium tuberculosis
    M C Schulbach
    Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA
    J Biol Chem 275:22876-81. 2000
    ..Previously, all known short chain isoprenyl diphosphate synthases catalyze the synthesis of products with E-stereochemistry...
  70. ncbi Interaction with the small subunit of geranyl diphosphate synthase modifies the chain length specificity of geranylgeranyl diphosphate synthase to produce geranyl diphosphate
    Charles Burke
    Institute of Biological Chemistry, Program in Plant Physiology, Washington State University, Pullman, Washington 99164 6340, USA
    J Biol Chem 277:3141-9. 2002
    ..Comparison of the kinetic behavior of the parent prenyltransferases with that of the hybrid enzyme revealed that the hybrid possesses characteristics of both geranyl diphosphate synthase and geranylgeranyl diphosphate synthase...
  71. pmc 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
    N Campos
    Department de Bioquimica i Biologia Molecular, Facultat de Quimica, Universitat de Barcelona, c Marti i Franques 1, 08028 Barcelona, Spain
    Biochem J 353:59-67. 2001
    ..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...
  72. ncbi Functional analysis of eubacterial diterpene cyclases responsible for biosynthesis of a diterpene antibiotic, terpentecin
    Yoshimitsu Hamano
    Biotechnology Research Center, Toyama Prefectural University, Toyama 939 0398, Japan
    J Biol Chem 277:37098-104. 2002
    ..These results suggested that an actual reaction catalyzed by the ORF12 was the conversion of TDP into TTE in vivo...
  73. ncbi Structure, mechanism and function of prenyltransferases
    Po Huang Liang
    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    Eur J Biochem 269:3339-54. 2002
    ..For the enzymes involved in cyclic terpene biosynthesis, the structures and mechanisms of squalene cyclase, 5-epi-aristolochene synthase, pentalenene synthase, and trichodiene synthase are summarized...
  74. ncbi Cloning and characterization of Ginkgo biloba levopimaradiene synthase which catalyzes the first committed step in ginkgolide biosynthesis
    H G Schepmann
    Department of Chemistry, Rice University, Houston, Texas 77005, USA
    Arch Biochem Biophys 392:263-9. 2001
    ..This is the first cloned ginkgolide biosynthetic gene and the first in vitro observation of an isolated ginkgolide biosynthetic enzyme...
  75. ncbi Nucleotide sequence of the ERG12 gene of Saccharomyces cerevisiae encoding mevalonate kinase
    A Oulmouden
    Laboratoire de Biochimie et Genetique des Microorganismes, Universite de Poitiers, France
    Curr Genet 19:9-14. 1991
    ..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...
  76. ncbi Abietadiene synthase catalysis: conserved residues involved in protonation-initiated cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate
    Reuben J Peters
    Institute of Biological Chemistry, Washington State University, Pullman, Washington 99164 6340, USA
    Biochemistry 41:1836-42. 2002
    ..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...
  77. ncbi Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway
    P A Edwards
    Department of Biological Chemistry, University of California Los Angeles 90095, USA
    Annu Rev Biochem 68:157-85. 1999
    ..They regulate transcriptional and post-transcriptional events that in turn affect lipid synthesis, meiosis, apoptosis, developmental patterning, protein cleavage, and protein degradation...
  78. ncbi Bifunctional abietadiene synthase: mutual structural dependence of the active sites for protonation-initiated and ionization-initiated cyclizations
    Reuben J Peters
    Institute of Biological Chemistry, Washington State University, Pullman, Washington 99164 6340, USA
    Biochemistry 42:2700-7. 2003
    ..Thus, the two cyclization sites of abietadiene synthase cannot be dissected into catalytically distinct domains, and, therefore, abietadiene synthase is unlikely to have arisen by fusion of two previously independent genes...
  79. ncbi Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation
    S M Houten
    Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Emma Children s Hospital, and Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Cell Mol Life Sci 60:1118-34. 2003
    ..We review the molecular, biochemical and immunological aspects of MK deficiency and discuss the relations between isoprenoid biosynthesis and inflammation. Finally, we compare MK deficiency with other autoinflammatory syndromes...
  80. ncbi Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology
    C A Lesburg
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Science 277:1820-4. 1997
    ....
  81. ncbi 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
    Rey Ting Guo
    Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan
    J Biol Chem 280:20762-74. 2005
    ..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...
  82. pmc Exploring biosynthetic diversity with trichodiene synthase
    L Sangeetha Vedula
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Arch Biochem Biophys 466:260-6. 2007
    ....
  83. pmc 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
    Juan A Faraldos
    Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA
    Chembiochem 8:1826-33. 2007
    ....
  84. pmc 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 Kato
    Department of Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    J Bacteriol 181:2733-8. 1999
    ....
  85. pmc Novel polyisoprenyl phosphates block phospholipase D and human neutrophil activation in vitro and murine peritoneal inflammation in vivo
    Bruce D Levy
    Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Br J Pharmacol 146:344-51. 2005
    ..b>Polyisoprenyl phosphates (PIPPs) are constituents of human leukocyte membranes that regulate pivotal intracellular enzymes, such ..
  86. ncbi Atorvastatin inhibits angiotensin-converting enzyme induction in differentiating human macrophages
    Outi Saijonmaa
    Minerva Institute for Medical Research, Helsinki, Finland
    Am J Physiol Heart Circ Physiol 292:H1917-21. 2007
    ..The finding that atorvastatin inhibited ACE upregulation may represent a novel pleiotropic action and an additional beneficial effect of statins in treatment of cardiovascular disease...
  87. pmc Rho-dependent inhibition of the induction of connective tissue growth factor (CTGF) by HMG CoA reductase inhibitors (statins)
    M Eberlein
    Medizinische Klinik IV, , Loschgestrasse 8, D-91054 Erlangen, Germany
    Br J Pharmacol 133:1172-80. 2001
    ..The direct interference of statins with the synthesis of CTGF, a protein functionally related to the development of fibrosis, may thus be a novel mechanism underlying the beneficial effects of statins observed in renal diseases...
  88. pmc Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas
    Jim Dimitroulakos
    Department of Cellular and Molecular Biology, The University Health Network, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
    Neoplasia 4:337-46. 2002
    ..Our data suggest that the depletion of nonsterol mevalonate metabolites, particularly GGPP, can be potential mediators of lovastatin-induced apoptosis of HNSCC and CC cells...
  89. ncbi Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation
    B Wong
    Departments of. Lipid Biochemistry, Merck Research Laboratories, Rahway, New Jersey, USA
    J Leukoc Biol 69:959-62. 2001
    ..These data supported the role of geranylgeranylation in the migration and MMP-9 secretion of monocytes...
  90. ncbi Overexpression of the lemon basil alpha-zingiberene synthase gene increases both mono- and sesquiterpene contents in tomato fruit
    Rachel Davidovich-Rikanati
    Department of Vegetable Crops, Newe Ya ar Research Center, Agricultural Research Organization, P O Box 1021, Ramat Yishay 30095, Israel
    Plant J 56:228-38. 2008
    ....
  91. ncbi Simvastatin-induced endothelial cell detachment and microparticle release are prenylation dependent
    Michaela Diamant
    Department of Endocrinology Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands
    Thromb Haemost 100:489-97. 2008
    ..We hypothesize that by facilitating detachment and EMP release, statins improve the overall condition of the remaining vascular endothelium...
  92. ncbi Lovastatin and mevastatin reduce basal and cytokine-stimulated production of prostaglandins from rat microglial cells in vitro: evidence for a mechanism unrelated to the inhibition of hydroxy-methyl-glutaryl CoA reductase
    Giuseppe Tringali
    Institute of Pharmacology, Catholic University Medical School, Largo Francesco Vito 1, 00168 Rome, Italy
    Neurosci Lett 354:107-10. 2004
    ....
  93. ncbi Biochemical characterization of the decaprenyl diphosphate synthase of Rhodobacter sphaeroides for coenzyme Q10 production
    Hossein Shahbani Zahiri
    Department of Microbiology, Gyeongsang National University, Gazwa dong 900, Jinju 660 701, South Korea
    Appl Microbiol Biotechnol 73:796-806. 2006
    ..The kinetic parameters of V (max) (pmol/min), K (M) (microM), k (cat) (1/min), and k (cat) /K (M) of the enzyme using FPP as the most appropriate substrate were determined to be 264.6, 13.1, 8.8, and 0.67, respectively...
  94. ncbi Lovastatin induces apoptosis of spontaneously immortalized rat brain neuroblasts: involvement of nonsterol isoprenoid biosynthesis inhibition
    N García-Román
    Departamento de Bioquimica y Biologia Molecular, Departamento de Fisiologia, Universidad de Alcala, 28871 Alcala de Henares, Madrid, Spain
    Mol Cell Neurosci 17:329-41. 2001
    ....
  95. ncbi Isoprenoid depletion by statins antagonizes cytokine-induced down-regulation of endothelial nitric oxide expression and increases NO synthase activity in human umbilical vein endothelial cells
    F Jantzen
    Department of Internal Medicine B, Ernst Moritz Arndt University, Greifswald, Germany
    J Physiol Pharmacol 58:503-14. 2007
    ..These results provide evidence that statins have beneficial effects by increasing eNOS expression and activity during the atherosclerotic process...
  96. ncbi Atorvastatin neutralizes the up-regulation of thrombospondin-1 induced by thrombin in human umbilical vein endothelial cells
    Vicenta Martinez-Sales
    Research Centre, La Fe University Hospital, Valencia, Spain
    Endothelium 14:233-8. 2007
    ..Because FPP and GGPP are essential for the activity of Rho proteins, inhibition of these proteins may constitute the mechanism by which atorvastatin inhibits thrombin up-regulated TSP-1 expression...
  97. ncbi Coupling of isoprenoid triflates with organoboron nucleophiles: synthesis and biological evaluation of geranylgeranyl diphosphate analogues
    YongQi Mu
    Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA
    Bioorg Med Chem 10:1207-19. 2002
    ..Note that all four of the GGPP analogues were bound less tightly by the enzyme than the natural substrate, in contrast to the behavior of the 3-substituted FPP analogues...
  98. ncbi Lovastatin enhances ecto-5'-nucleotidase activity and cell surface expression in endothelial cells: implication of rho-family GTPases
    S Ledoux
    INSERM U426, Faculte de Medecine Xavier Bichat, Universite Paris, France
    Circ Res 90:420-7. 2002
    ..This effect seems independent of lowering cholesterol content but could be supported by an inhibition of Ecto-5'-Nu endocytosis through a decrease of Rho-GTPases isoprenylation...
  99. ncbi Decreased C-reactive protein-induced resistin production in human monocytes by simvastatin
    Wen Lan Hu
    Department of Cardiology, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, PR China
    Cytokine 40:201-6. 2007
    ..We hypothesize that CRP may result in overexpression of resistin, and statin may decrease CRP-induced resistin expression in cultured human peripheral blood monocytes (PBMC)...
  100. ncbi Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells
    Z Xia
    Department of Cellular and Molecular Biology, Ontario Cancer Institute, University Health Network, Toronto, Canada
    Leukemia 15:1398-407. 2001
    ..We conclude that blockage of the mevalonate pathway, particularly inhibition of protein geranylgeranylation holds a critical role in the mechanism of lovastatin-induced apoptosis in AML cells...
  101. ncbi Isolation and functional characterization of a beta-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith
    Fengnian Yu
    Department of Bioscience, Graduate School of Agriculture, Kinki University, Nakamachi, Nara, Japan
    FEBS Lett 582:565-72. 2008
    ..coli and coexpressed it with ZSS2. When supplemented with mevalonate, the engineered E. coli produced a similar sesquiterpene profile to that produced in the in vitro enzyme assay, and the yield of beta-eudesmol reached 100 mg/L...

Research Grants23

  1. Role of PI3-Kinase in Estrogen-induced eNOS Activation
    James Liao; Fiscal Year: 2007
    ..These results may explain some of the actions of selective estrogen receptor modulators (SERMs) and provide a therapeutic basis for using estrogens in cardiovascular disease. ..
  2. Activation of eNOS by Steroid Hormones
    James Liao; Fiscal Year: 2006
    ....
  3. Endothelial Akt in Vascular Injury
    James Liao; Fiscal Year: 2009
    ..Three specific aims are proposed, which will study the role of endothelial Akt in models of vascular injury and atherosclerosis. ..
  4. Structure/Function of Peroxisomes in Neuroinflammation
    Inderjit Singh; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  5. GGPP-mediated modulation of APP processing
    Yan Zhou; Fiscal Year: 2008
    ..We will be able to define the underlying mechanisms through proposed studies, thus providing new drug targets for the prevention and treatment of Alzheimer's disease. [unreadable] [unreadable] [unreadable]..
  6. Remodeling of the M. tuberculosis cell wall during infection
    DAVID BRANCH MOODY; Fiscal Year: 2010
    ..Identification of the genes, enzymes and cell wall lipids that mediate adaptation to growth in tissues provides the information necessary to achieve this goal. ..
  7. Identification of Genes Activated by Bile Acids
    Peter Edwards; Fiscal Year: 2009
    ..In addition, these studies will elucidate the role of FXR in glucose, steroid and drug metabolism and in resistance to endotoxin. ..
  8. Regulation of Neuronal Survival by the Rit GTPase
    Douglas Andres; Fiscal Year: 2008
    ..Regulation of this novel Ras-related G-protein may have a pronounced impact on neuronal physiology and would make Rit and its effectors, potential targets for the development of new therapeutic strategies. ..
  9. Regulation of Bile Acid Synthesis by Nuclear Receptors
    John Y L Chiang; Fiscal Year: 2010
    ..This study could contribute to understanding the mechanisms of metabolic diseases caused by dysregulation of bile acid synthesis and develop therapeutic agents to treat dyslipidemia, liver diseases, obesity and type II diabetes. ..
  10. Oxidative Stress and Anti-Inflammatory Lipids in Airway Disease
    Bruce D Levy; Fiscal Year: 2010
    ..In this proposal, we seek to develop a better understanding of the natural biological processes invoked during airway infection and inflammation that dysregulate the natural homeostatic mechanisms. (End of Abstract) ..
  11. TRYPANOSOMA CRUZI MUCOSAL & SYSTEMIC PROTECTIVE IMMUNITY
    DANIEL HOFT; Fiscal Year: 2008
    ..Chemokine and/or integrin receptor expression will be studied by flow cytometry and RT-Real-Time PCR, and the in vivo effects of defective chemokine and integrin binding and/or signaling will be evaluated. [unreadable] [unreadable]..
  12. Lipid Mediators in the Resolution of Asthma Exacerbations
    Bruce Levy; Fiscal Year: 2008
    ..This proposal's specific aims are directed towards uncovering basic mechanisms in the pathobiology of resolution from asthma exacerbation. ..
  13. ANTIGEN RECOGNITION BY GAMMA DELTA T CELLS
    CRAIG MORITA; Fiscal Year: 2007
    ..These studies will provide insights into nonpeptide antigen recognition by human gammadelta T cells and should help clarify their role in immunity and autoimmunity. ..
  14. NOVEL LUNG DERIVED CHALONES--BIOSYNTHESIS AND BIOACTIONS
    Bruce Levy; Fiscal Year: 2002
    ..End of Abstract) ..
  15. NEW METHODS FOR THE SYNTHESIS OF BIOACTIVE MOLECULES
    NICOS PETASIS; Fiscal Year: 2003
    ..Therefore, this program makes new advances in organic, medicinal and combinatorial chemistry, and enhances the role of organic synthesis in biomedical research. ..
  16. Vaccine Induced Mucosal Protection Against TB Infection
    DANIEL HOFT; Fiscal Year: 2005
    ..Prime/boosting strategies found to prevent BCG infection after aerosol challenges will be studied for the ability to prevent infection with virulent M. tuberculosis by aerosol challenge. ..
  17. STRUCTURE/FUNCTION OF EPOXIDE HYDROLASE
    David Christianson; Fiscal Year: 2005
    ..abstract_text> ..
  18. Mechanism of Actions of Multitasking of Statins in AD
    Inderjit Singh; Fiscal Year: 2006
    ..abstract_text> ..
  19. The Role of Tuberin in Smooth Muscle Cell Proliferation
    Geraldine Finlay; Fiscal Year: 2007
    ..abstract_text> ..
  20. STRUCTURE/FUNCTION OF CARBONIC ANHYDRASE
    David Christianson; Fiscal Year: 2001
    ..The proposed work will answer the question: what structural features constitute an effective catalytic proton shuttle site in an enzyme? ..
  21. Immunotherapy with Gamma Delta T Cells for B Cell Tumors
    CRAIG MORITA; Fiscal Year: 2008
    ..abstract_text> ..
  22. CHARACTERIZATION OF THE PRELAMIN A ENDOPROTEASE
    Michael Sinensky; Fiscal Year: 2001
    ..abstract_text> ..