pyrophosphatases

Summary

Summary: A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-.

Top Publications

  1. pmc Salicylic acid-independent ENHANCED DISEASE SUSCEPTIBILITY1 signaling in Arabidopsis immunity and cell death is regulated by the monooxygenase FMO1 and the Nudix hydrolase NUDT7
    Michael Bartsch
    Department of Plant Microbe Interactions, Max Planck Institute for Plant Breeding Research, D 50829 Cologne, Germany
    Plant Cell 18:1038-51. 2006
  2. ncbi The Nudix hydrolase superfamily
    A G McLennan
    School of Biological Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, United Kingdom
    Cell Mol Life Sci 63:123-43. 2006
  3. ncbi MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis
    H Maki
    Department of Biochemistry, Faculty of Medicine, Kyushu University, Fukuoka, Japan
    Nature 355:273-5. 1992
  4. ncbi Counteraction by MutT protein of transcriptional errors caused by oxidative damage
    F Taddei
    Institut Jacques Monod, Tour 43, 2 place Jussieu, 75251 Paris Cedex 05, France
    Science 278:128-30. 1997
  5. ncbi The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes
    M J Bessman
    Department of Biology and The McCollum Pratt Institute, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Biol Chem 271:25059-62. 1996
  6. ncbi ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C
    Jacques Fellay
    Institute for Genome Sciences and Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA
    Nature 464:405-8. 2010
  7. ncbi Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C
    Yasuhito Tanaka
    Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    Hum Mol Genet 20:3507-16. 2011
  8. pmc Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders
    Dympna Harmey
    The Burnham Institute, La Jolla, CA 92037, USA
    Am J Pathol 164:1199-209. 2004
  9. ncbi (p)ppGpp: still magical?
    Katarzyna Potrykus
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2785, USA
    Annu Rev Microbiol 62:35-51. 2008
  10. pmc Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production
    Makiko Umezu-Goto
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Cell Biol 158:227-33. 2002

Research Grants

  1. BIOENERGETICS AND PROTON PUMPS IN MALARIA PARASITES
    Akhil Vaidya; Fiscal Year: 2007
  2. Structure, Function and Mechanism of Nudix Hydrolases
    L Amzel; Fiscal Year: 2006
  3. Novel Cap Analogs and Interactions with Target Proteins
    ROBERT RHOADS; Fiscal Year: 2005
  4. GLUTAMINE AMIDOTRANSFERASES AND PARTNER ENZYMES
    Janet Smith; Fiscal Year: 2007
  5. PHOSPHOLIPID METABOLISM AND MEMBRANE FUNCTION
    GEORGE CARMAN; Fiscal Year: 2009
  6. Computational Approach to Ligand Discovery for LPA GPCR and PPAR
    Abby L Parrill; Fiscal Year: 2010
  7. ANK and Joint Ankylosis in Spondylitis
    Robert Terkeltaub; Fiscal Year: 2008
  8. ROLE OF DUTPASE EXPRESSION IN CANCER CHEMOTHERAPY
    Robert Ladner; Fiscal Year: 2003
  9. PTHRP 1 to 173 IN CHONDROCYTES
    Robert Terkeltaub; Fiscal Year: 2005
  10. dUTPase As A Prognostic Marker in Colon Cancer
    Robert Ladner; Fiscal Year: 2003

Detail Information

Publications282 found, 100 shown here

  1. pmc Salicylic acid-independent ENHANCED DISEASE SUSCEPTIBILITY1 signaling in Arabidopsis immunity and cell death is regulated by the monooxygenase FMO1 and the Nudix hydrolase NUDT7
    Michael Bartsch
    Department of Plant Microbe Interactions, Max Planck Institute for Plant Breeding Research, D 50829 Cologne, Germany
    Plant Cell 18:1038-51. 2006
    ..We find instead that SA antagonizes initiation of cell death and stunting of growth in nudt7 mutants...
  2. ncbi The Nudix hydrolase superfamily
    A G McLennan
    School of Biological Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, United Kingdom
    Cell Mol Life Sci 63:123-43. 2006
    ....
  3. ncbi MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis
    H Maki
    Department of Biochemistry, Faculty of Medicine, Kyushu University, Fukuoka, Japan
    Nature 355:273-5. 1992
    ..This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis...
  4. ncbi Counteraction by MutT protein of transcriptional errors caused by oxidative damage
    F Taddei
    Institut Jacques Monod, Tour 43, 2 place Jussieu, 75251 Paris Cedex 05, France
    Science 278:128-30. 1997
    ..Such control of transcriptional fidelity by the ubiquitous MutT function has implications for evolution of RNA-based life, phenotypic expression, adaptive mutagenesis, and functional maintenance of nondividing cells...
  5. ncbi The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes
    M J Bessman
    Department of Biology and The McCollum Pratt Institute, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Biol Chem 271:25059-62. 1996
  6. ncbi ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C
    Jacques Fellay
    Institute for Genome Sciences and Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA
    Nature 464:405-8. 2010
    ..Here we show that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against haemolytic anaemia in hepatitis-C-infected patients receiving RBV...
  7. ncbi Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C
    Yasuhito Tanaka
    Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    Hum Mol Genet 20:3507-16. 2011
    ..Our present results may provide a valuable pharmacogenetic diagnostic tool for tailoring PEG-IFN/RBV dosing to minimize drug-induced adverse events...
  8. pmc Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders
    Dympna Harmey
    The Burnham Institute, La Jolla, CA 92037, USA
    Am J Pathol 164:1199-209. 2004
    ..The hypomineralization observed in Akp2(-/-) mice arises from the combined inhibitory effects of PP(i) and OPN. In contrast, NPP1 or ANK deficiencies cause a decrease in the PP(i) and OPN pools that leads to hypermineralization...
  9. ncbi (p)ppGpp: still magical?
    Katarzyna Potrykus
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2785, USA
    Annu Rev Microbiol 62:35-51. 2008
    ..Many basic questions still exist. This review tries to focus on some issues that linger even for the most widely characterized bacterial strains...
  10. pmc Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production
    Makiko Umezu-Goto
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Cell Biol 158:227-33. 2002
    ..It also provides potential novel targets for therapy of pathophysiological states including cancer...
  11. ncbi Regulation and biological activities of the autotaxin-LPA axis
    Laurens A van Meeteren
    Division of Cellular Biochemistry, Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
    Prog Lipid Res 46:145-60. 2007
    ....
  12. pmc Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development
    Laurens A van Meeteren
    Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cell Biol 26:5015-22. 2006
    ....
  13. ncbi The ins and outs of lysophosphatidic acid signaling
    Wouter H Moolenaar
    Division of Cellular Biochemistry and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan, Amsterdam, The Netherlands
    Bioessays 26:870-81. 2004
    ..Exogenous phospholipases D can also produce LPA, which may contribute to their toxicity. Here we review recent progress in our understanding of LPA bioactivity, signaling and synthesis...
  14. ncbi Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine
    A Okawa
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan
    Nat Genet 19:271-3. 1998
    ..Our results may lead to novel insights into the mechanism of ectopic ossification and the aetiology of human OPLL...
  15. ncbi Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase
    Akira Tokumura
    Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770 8505, Japan
    J Biol Chem 277:39436-42. 2002
    ....
  16. pmc Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes
    David Meyre
    CNRS 8090 Institute of Biology, Pasteur Institute, Lille, France
    Nat Genet 37:863-7. 2005
    ..These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions...
  17. ncbi Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification
    Frank Rutsch
    Department of Medicine, Veterans Affairs Medical Center, University of California San Diego, 3350 La Jolla Village Drive, La Jolla, California 92161, USA
    Nat Genet 34:379-81. 2003
    ..This cell surface enzyme generates inorganic pyrophosphate (PP(i)), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification...
  18. ncbi Insulin signaling regulating genes: effect on T2DM and cardiovascular risk
    Sabrina Prudente
    IRCCS Casa Sollievo della Sofferenza, Mendel Institute, Rome, Italy
    Nat Rev Endocrinol 5:682-93. 2009
    ..Unraveling the role of such variants might be facilitated by improving disease definition and focusing on specific subsets of patients...
  19. ncbi Genetics in arterial calcification: lessons learned from rare diseases
    Yvonne Nitschke
    Department of General Pediatrics, Münster University Children s Hospital, D 48149 Munster, Germany
    Trends Cardiovasc Med 22:145-9. 2012
    ....
  20. pmc The role of membrane glycoprotein plasma cell antigen 1/ectonucleotide pyrophosphatase phosphodiesterase 1 in the pathogenesis of insulin resistance and related abnormalities
    Ira D Goldfine
    Department of Medicine and Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
    Endocr Rev 29:62-75. 2008
    ..These data suggest therefore that PC-1 is a candidate protein that may play a role in human insulin resistance and T2D by its overexpression, its overactivity, or both...
  21. ncbi ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology
    A L Perraud
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 411:595-9. 2001
    ..domain) near the carboxy terminus of the LTRPC2/TrpC7 putative cation channel both function as specific ADPR pyrophosphatases. Whole-cell and single-channel analysis of HEK-293 cells expressing LTRPC2 show that LTRPC2 functions as a ..
  22. pmc Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets
    Bettina Lorenz-Depiereux
    Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
    Am J Hum Genet 86:267-72. 2010
    ..Surprisingly, ENPP1 loss-of-function mutations have previously been described in generalized arterial calcification of infancy, suggesting an as yet elusive mechanism that balances arterial calcification with bone mineralization...
  23. ncbi NPP-type ectophosphodiesterases: unity in diversity
    Cristiana Stefan
    Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Trends Biochem Sci 30:542-50. 2005
    ..NPP-type ectophosphodiesterases are also implicated in the pathophysiology of cancer, insulin resistance and calcification diseases, and they hold great promise as easily accessible therapeutic targets...
  24. ncbi Inorganic pyrophosphate generation and disposition in pathophysiology
    R A Terkeltaub
    Veterans Affairs Medical Center and School of Medicine, University of California, San Diego, California 92161, USA
    Am J Physiol Cell Physiol 281:C1-C11. 2001
    ....
  25. pmc Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene
    Varda Levy-Litan
    Department of Developmental Genetics and Virology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
    Am J Hum Genet 86:273-8. 2010
    ..Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1...
  26. pmc A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase
    S T Safrany
    Inositide Signaling Group, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, PO Box 12233, NC 27709, USA
    EMBO J 17:6599-607. 1998
    ..Because overlapping substrate specificity is a feature of this class of proteins, our data provide new directions for future studies of higher inositol phosphates...
  27. pmc Uracil-containing DNA in Drosophila: stability, stage-specific accumulation, and developmental involvement
    Villo Muha
    Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Science, Budapest, Hungary
    PLoS Genet 8:e1002738. 2012
    ..Importantly, we also show lack of the UNG gene in all available genomes of other Holometabola insects, indicating a potentially general tolerance and developmental role of uracil-DNA in this evolutionary clade...
  28. ncbi Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1
    Kotaro Hama
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Biol Chem 279:17634-9. 2004
    ..The present study suggests that ATX and LPA(1) represent potential targets for cancer therapy...
  29. ncbi A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene
    Tasuku Saito
    Division of Pediatrics, University of Tokyo Hospital, Tokyo, Japan
    Bone 49:913-6. 2011
    ..Because Enpp1 knockout mouse is a model of OPLL, this case also suggests that OPLL is associated with ARHR2...
  30. ncbi Increased uracil insertion in DNA is cytotoxic and increases the frequency of mutation, double strand break formation and VSG switching in Trypanosoma brucei
    Victor M Castillo-Acosta
    Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Cientificas, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, s n 18100 Armilla, Granada, Spain
    DNA Repair (Amst) 11:986-95. 2012
    ..brucei to uracil in DNA emphasizes the importance of uracil removal and regulation of intracellular dUTP pool levels in cell viability and genetic stability and suggests potential strategies to compromise parasite survival...
  31. ncbi Molecular actions of Escherichia coli MutT for control of spontaneous mutagenesis
    Daiki Setoyama
    Advanced Science Research Center, Fukuoka Dental College, Sawara ku, Fukuoka 814 0193, Japan
    Mutat Res 707:9-14. 2011
    ..There is a possibility that MutT functions in close association with other proteins, and evidence is presented that MutT protein can interact with some proteins in vivo...
  32. pmc Mammalian enzymes for preventing transcriptional errors caused by oxidative damage
    Toru Ishibashi
    Biomolecular Engineering Research Institute Suita, Osaka 565 0874, Japan
    Nucleic Acids Res 33:3779-84. 2005
    ..These results indicate that the elimination of 8-oxoGua-containing ribonucleotides from the precursor pool is important to ensure accurate protein synthesis and that both NUDT5 and MTH1 are involved in this process in human cells...
  33. pmc Mycobacterial MazG is a novel NTP pyrophosphohydrolase involved in oxidative stress response
    Liang dong Lu
    State Key Laboratory of Genetic Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China
    J Biol Chem 285:28076-85. 2010
    ..Our work implicates a role for the MazG activity in the virulence of M. tuberculosis...
  34. ncbi The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121)
    B V Costanzo
    Institute of Internal Medicine, Endocrine and Metabolic Diseases, University of Catania, Ospedale Garibaldi, Italy
    Diabetes 50:831-6. 2001
    ....
  35. pmc Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators
    Dmitry A Rodionov
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Nucleic Acids Res 36:2047-59. 2008
    ..family (here termed NrtR for Nudix-related transcriptional regulators), currently annotated as ADP-ribose pyrophosphatases from the Nudix family, are composed of an N-terminal Nudix-like effector domain and a C-terminal DNA-binding ..
  36. ncbi Substrate specificity and membrane topology of Escherichia coli PgpB, an undecaprenyl pyrophosphate phosphatase
    Thierry Touze
    Universite Paris Sud, UMR 8619, Institut de Biochimie et Biophysique Moléculaire et Cellulaire and CNRS, Laboratoire des Enveloppes Bactériennes et Antibiotiques, UMR 8619, 91405 Orsay Cedex, France
    J Biol Chem 283:16573-83. 2008
    ..Furthermore, a topological analysis demonstrated that PgpB contains six transmembrane segments, a large periplasmic loop, and the type 2 phosphatidic acid phosphatase signature residues at a periplasmic location...
  37. pmc Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases
    Beata G Vertessy
    Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary
    Acc Chem Res 42:97-106. 2009
    ..In these respective pathogens, Plasmodium falciparum and Mycobacterium tuberculosis, the biosynthesis of dTMP relies exclusively on dUTPase activity...
  38. ncbi Distribution of ITPA P32T alleles in multiple world populations
    Sharon Marsh
    Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St Louis, MO 63110, USA
    J Hum Genet 49:579-81. 2004
    ..This data provides a foundation on which prospective screening studies can be planned to identify patients at risk for severe toxicity from azathioprine therapy...
  39. pmc Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization
    Lovisa Hessle
    The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:9445-9. 2002
    ..Our results suggest that inhibiting PC-1 function may be a viable therapeutic strategy for hypophosphatasia. Conversely, interfering with TNAP activity may correct pathological hyperossification because of PP(i) insufficiency...
  40. pmc The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life
    Gemma C Atkinson
    University of Tartu, Institute of Technology, Tartu, Estonia
    PLoS ONE 6:e23479. 2011
    ..Such signals may be transmitted via NTD to CTD intra-molecular interactions, or inter-molecular interactions either among individual RSH molecules or among long RSHs and other binding partners such as the ribosome...
  41. pmc AVP2, a sequence-divergent, K(+)-insensitive H(+)-translocating inorganic pyrophosphatase from Arabidopsis
    Y M Drozdowicz
    Plant Science Institute, Department of Biology, University of Pennsylvania, Philadelphia 19104 6018, USA
    Plant Physiol 123:353-62. 2000
    Plant vacuolar H(+)-translocating inorganic pyrophosphatases (V-PPases; EC 3.6.1.1) have been considered to constitute a family of functionally and structurally monotonous intrinsic membrane proteins. Typified by AVP1 (V. Sarafian, Y...
  42. ncbi Inosine triphosphate protects against ribavirin-induced adenosine triphosphate loss by adenylosuccinate synthase function
    Yuki Hitomi
    Center for Human Genome Variation, School of Medicine, Duke University, Durham, North Carolina, USA
    Gastroenterology 140:1314-21. 2011
    ..However, the biologic mechanism by which this occurs is unknown...
  43. ncbi Gene expression profiles of lysophosphatidic acid-related molecules in the prostate: relevance to prostate cancer and benign hyperplasia
    Yu Zeng
    Department of Urology, Kagawa University Faculty of Medicine, Kita gun, Kagawa, Japan
    Prostate 69:283-92. 2009
    ..To elucidate gene expression profiles of lysophosphatidic acid (LPA)-related molecules in cancer, pre-cancerous lesion, and benign hyperplasia of the prostate...
  44. ncbi The expression of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (E-NPP1) is correlated with astrocytic tumor grade
    Indra Aerts
    Department of Biomedical Science, Cellular Biochemistry, Campus Drie Eiken, University of Antwerp, Belgium
    Clin Neurol Neurosurg 113:224-9. 2011
    ..In this study, the use of anti-NPP1 antibody in the determination of astrocytic tumor grade is evaluated...
  45. ncbi Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase)
    Anthony M Marinaki
    Purine Research Laboratory, Department of Chemical Pathology and Department of Gastroenterology, Guy s and St Thomas Hospital, London, UK
    Pharmacogenetics 14:181-7. 2004
    ..5, 95% CI 1.4-21.3, P = 0.0206). Polymorphism in the ITPA gene predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency...
  46. ncbi The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site
    Rik Gijsbers
    Afdeling Biochemie, Faculteit Geneeskunde, University of Leuven, Herestraat 49, B 3000 Leuven, Belgium
    FEBS Lett 538:60-4. 2003
    ..In comparing the substrate specificity of NPP2 and the closely related NPP1 and NPP3, we found that only NPP2 displayed a lysophospholipase D activity, whereas NPP1 and NPP3 had a much higher nucleotide pyrophosphatase activity...
  47. pmc dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae
    Marie Guillet
    CEA, DSV Département de Radiobiologie et Radiopathologie, UMR 217 CNRS Radiobiologie Moléculaire et Cellulaire, BP 6, 92265 Fontenay aux Roses, France
    Nucleic Acids Res 34:2056-66. 2006
    ..Therefore, the normal cellular metabolism, and not only its byproducts, is an important source of endogenous DNA damage and genetic instability in eukaryotic cells...
  48. ncbi Cost of unneeded proteins in E. coli is reduced after several generations in exponential growth
    Irit Shachrai
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Mol Cell 38:758-67. 2010
    ....
  49. pmc Role of the ENPP1 K121Q polymorphism in glucose homeostasis
    Roberto Baratta
    Unit of Endocrinology, Department of Internal and Specialistic Medicine, University of Catania Medical School, Garibaldi Hospital, Catania, Italy
    Diabetes 57:3360-4. 2008
    ..To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy...
  50. ncbi Discovery and optimization of boronic acid based inhibitors of autotaxin
    Harald M H G Albers
    Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    J Med Chem 53:4958-67. 2010
    ..The most potent of these compounds inhibits ATX-mediated LPC hydrolysis in the nanomolar range (IC(50) = 6 nM). The finding that ATX can be targeted by boronic acids may aid the development of ATX inhibitors for therapeutic use...
  51. pmc Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation
    Harald M H G Albers
    Division of Cell Biology, Netherlands Proteomics Centre, Centre of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 107:7257-62. 2010
    ..Thus, boronic acid-based small molecules hold promise as candidate drugs to target ATX...
  52. pmc Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia
    G Stocco
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Clin Pharmacol Ther 85:164-72. 2009
    ....
  53. ncbi Pharmacogenetic significance of inosine triphosphatase
    Jörgen Bierau
    Maastricht University Hospital, Laboratory of Biochemical Genetics, Department of Clinical Genetics, PO Box 6202 AZ Maastricht, The Netherlands
    Pharmacogenomics 8:1221-8. 2007
    ..However, the present state of knowledge is still insufficient to definitively determine the pharmacogenetic significance of ITPase. This article aims to review the current knowledge on the role of ITPase in thiopurine metabolism...
  54. pmc Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands
    María Angeles Tormo-Más
    Centro de Investigación y Tecnología Animal, Instituto Valenciano de Investigaciones Agrarias CITA IVIA, Apdo 187, Segorbe, Castellón 12400, Spain
    Nature 465:779-82. 2010
    ..The highly specific interactions between different SaPI repressors and helper-phage-encoded antirepressors represent a remarkable evolutionary adaptation involved in pathogenicity island mobilization...
  55. ncbi The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein
    K Fujikawa
    Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1 1 Iseigaoka, Yahatanishi ku, Kitakyushu 807 8555, Japan
    J Biol Chem 274:18201-5. 1999
    ..These results suggest that the three damaged nucleotides share the same recognition site of hMTH1 and that it is a more important sanitization enzyme than expected thus far...
  56. ncbi Altered subunit communication in subfamilies of trimeric dUTPases
    A Fiser
    Rockefeller University, New York, New York, 10021, USA
    Biochem Biophys Res Commun 279:534-42. 2000
    ..Results allow clear distinction between two subfamilies of trimeric dUTPases where altered subunit communication may account for a functional difference in the catalytic cycle...
  57. ncbi House cleaning, a part of good housekeeping
    Michael Y Galperin
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
    Mol Microbiol 59:5-19. 2006
    ..House-cleaning NTP pyrophosphatases targeting non-canonical NTPs belong to at least four structural superfamilies: MutT-related (Nudix) ..
  58. pmc Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases
    Shuying Liu
    Department of Systems Biology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Cell 15:539-50. 2009
    ..Thus, ATX and LPA receptors can contribute to the initiation and progression of breast cancer...
  59. pmc Inhibition of autotaxin production or activity blocks lysophosphatidylcholine-induced migration of human breast cancer and melanoma cells
    Cristoforo G Gaetano
    Department of Biochemistry, Signal Transduction Research Group, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
    Mol Carcinog 48:801-9. 2009
    ..We conclude that inhibiting autotaxin production or activity could provide a beneficial adjuvant to chemotherapy for preventing tumor growth and metastasis in patients with high autotaxin expression in their tumors...
  60. pmc Sustained osteomalacia of long bones despite major improvement in other hypophosphatasia-related mineral deficits in tissue nonspecific alkaline phosphatase/nucleotide pyrophosphatase phosphodiesterase 1 double-deficient mice
    H Clarke Anderson
    Dept of Pathology and Lab Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA
    Am J Pathol 166:1711-20. 2005
    ..Thus, the osteomalacia of Akp2-/- mice and the hypomineralized phenotype of the long bones of Enpp1-/- mice are not rescued by simultaneous deletion of TNAP and NPP1 functions...
  61. pmc ATX-LPA receptor axis in inflammation and cancer
    Shuying Liu
    Department of Systems Biology, University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Cell Cycle 8:3695-701. 2009
    ....
  62. ncbi Structural and catalytic similarities between nucleotide pyrophosphatases/phosphodiesterases and alkaline phosphatases
    R Gijsbers
    Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    J Biol Chem 276:1361-8. 2001
    Nucleotide pyrophosphatases/phosphodiesterases (NPPs) generate nucleoside 5'-monophosphates from a variety of nucleotides and their derivatives...
  63. ncbi Autotaxin protects MCF-7 breast cancer and MDA-MB-435 melanoma cells against Taxol-induced apoptosis
    N Samadi
    Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
    Oncogene 28:1028-39. 2009
    ..Our results support the hypothesis that therapeutic inhibition of ATX activity could improve the efficacy of Taxol as a chemotherapeutic agent for cancer treatment...
  64. ncbi Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid
    Yasuhiro Kishi
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033
    J Biol Chem 281:17492-500. 2006
    ....
  65. ncbi Structures and mechanisms of Nudix hydrolases
    A S Mildvan
    Department of Biological Chemistry, The Johns Hopkins School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205 2185, USA
    Arch Biochem Biophys 433:129-43. 2005
    ..The overall rate accelerations can be explained by both independent and cooperative effects of these catalytic components...
  66. ncbi Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit
    B A Maddux
    Department of Medicine, Mount Zion Medical Center, University of California San Francisco, USA
    Diabetes 49:13-9. 2000
    ..These studies also raise the possibility that monoclonal antibodies to PC-1 could be a new treatment for insulin resistance...
  67. ncbi ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes
    Nicola Abate
    Department of Medicine, Division of Endocrinology and Metabolism and The Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9169, USA
    Diabetes 54:1207-13. 2005
    ....
  68. ncbi The EBV-encoded dUTPase activates NF-kappa B through the TLR2 and MyD88-dependent signaling pathway
    Maria Eugenia Ariza
    Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
    J Immunol 182:851-9. 2009
    ....
  69. ncbi Overexpression of an ADP-ribose pyrophosphatase, AtNUDX2, confers enhanced tolerance to oxidative stress in Arabidopsis plants
    Takahisa Ogawa
    Department of Advanced Bioscience, Faculty of Agriculture, Kinki University, 3327 204 Nakamachi, Nara 631 8505, Japan
    Plant J 57:289-301. 2009
    ....
  70. ncbi Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate
    Timothy Clair
    Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 63:5446-53. 2003
    ....
  71. ncbi EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease
    Ronald Glaser
    Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, 333 W 10th Avenue, Columbus, OH 43210, USA
    Virology 346:205-18. 2006
    ..The data support the hypothesis that at least one protein of the EBV early antigen complex can induce immune dysregulation and may be involved in the pathophysiology of EBV-associated disease...
  72. pmc dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae
    M H Gadsden
    Department of Biology, York University, Toronto, Ontario, Canada
    EMBO J 12:4425-31. 1993
    ..These results are in general agreement with previous models in thymine-less death that implicate dUTP metabolism. They also suggest an alternative approach for chemotherapeutic drug design...
  73. ncbi Three gene products govern (p)ppGpp production by Streptococcus mutans
    JOSE A LEMOS
    Department of Oral Biology, University of Florida College of Dentistry, PO Box 100424, Gainesville, FL 32610, USA
    Mol Microbiol 65:1568-81. 2007
    ....
  74. pmc Lysophospholipids in the limelight: autotaxin takes center stage
    Wouter H Moolenaar
    Division of Cellular Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Cell Biol 158:197-9. 2002
    ..This result is surprising, as there was previously no indication that autotaxin could act as a phospholipase...
  75. pmc PCPH/ENTPD5 expression confers to prostate cancer cells resistance against cisplatin-induced apoptosis through protein kinase Calpha-mediated Bcl-2 stabilization
    Joaquin Villar
    Laboratory of Experimental Carcinogenesis, Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road Northwest, Washington, DC 20057 1482, USA
    Cancer Res 69:102-10. 2009
    ....
  76. ncbi Kinetic characterization of dUTPase from Escherichia coli
    G Larsson
    Department of Biochemistry, Center for Chemistry and Chemical Engineering, Lund University, Lund, Sweden
    J Biol Chem 271:24010-6. 1996
    ..The results are discussed with reference to recent data on the structure of the E. coli dUTPase.UDP complex...
  77. ncbi Differential ectonucleotidase expression in human bladder cancer cell lines
    Joseli Stella
    Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
    Urol Oncol 28:260-7. 2010
    ..Our results open new avenues for research into the physiological roles of this family of enzymes and their possible therapeutic potential in bladder cancer...
  78. ncbi Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease
    Jun Hirose
    Medical College of Wisconsin, Milwaukee
    Arthritis Rheum 46:3218-29. 2002
    ....
  79. pmc Function and metabolism of sirtuin metabolite O-acetyl-ADP-ribose
    Lei Tong
    Department of Biomolecular Chemistry, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53706, USA
    Biochim Biophys Acta 1804:1617-25. 2010
    ..With recently developed tools, the pace of new discoveries of OAADPr-dependent processes should facilitate new molecular insight into the diverse biological processes modulated by sirtuins...
  80. ncbi Roles of uracil-DNA glycosylase and dUTPase in virus replication
    Renxiang Chen
    Department of Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research, and Comprehensive Cancer Center, Ohio State University Medical Center, 2078 Graves Hall, 333 West 10th Ave, Columbus, OH 43210, USA
    J Gen Virol 83:2339-45. 2002
    ..An understanding at the molecular level of how these viruses replicate in non-dividing cells should provide clues to the biological relevance of UNG and dUTPase function in virus replication...
  81. pmc Molecular cloning and sequence of cDNA encoding the pyrophosphate-energized vacuolar membrane proton pump of Arabidopsis thaliana
    V Sarafian
    Department of Biology, University of Pennsylvania, Philadelphia 19104
    Proc Natl Acad Sci U S A 89:1775-9. 1992
    ..The lack of sequence identities between the tonoplast H(+)-PPase and any other characterized H+ pump or PPi-dependent enzyme implies a different evolutionary origin for this translocase...
  82. ncbi dUTPase from the retrovirus equine infectious anemia virus: specificity, turnover and inhibition
    J Nord
    Department of Biochemistry, Center for Chemistry and Chemical Engineering, University of Lund, Sweden
    FEBS Lett 414:271-4. 1997
    ..Inhibition of the viral enzyme by the nucleotides dTTP, dUMP and a synthetic analogue, 2'-deoxyuridine 5'-(alpha,beta-imido)triphosphate, is stronger by one order of magnitude...
  83. pmc The dUTPase enzyme is essential in Mycobacterium smegmatis
    Ildiko Pecsi
    Institute of Enzymology, RCNS, Hungarian Academy of Sciences, Budapest, Hungary
    PLoS ONE 7:e37461. 2012
    ..Our results indicate the potential of dUTPase as a target for antitubercular drugs and identify a genus-specific surface loop on the enzyme as a selective target...
  84. ncbi Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer
    Peter M Wilson
    Department of Pathology, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, University of Southern California, Los Angeles, CA 90089, USA
    Mol Cancer Ther 11:616-28. 2012
    ....
  85. ncbi The NADH diphosphatase encoded by the Saccharomyces cerevisiae NPY1 nudix hydrolase gene is located in peroxisomes
    S R AbdelRaheim
    School of Biological Sciences, University of Liverpool, United Kingdom
    Arch Biochem Biophys 388:18-24. 2001
    ..This function may be the regulation of nicotinamide coenzyme concentrations independently of those in other compartments or the elimination of oxidized nucleotide derivatives from the peroxisomal environment...
  86. pmc Nucleotide pyrophosphatase employs a P-loop-like motif to enhance catalytic power and NDP/NTP discrimination
    Ildiko Pecsi
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, H 1113, Budapest, Karolina ut 29, Hungary
    Proc Natl Acad Sci U S A 108:14437-42. 2011
    We investigated the potential (d)NDP/(d)NTP discrimination mechanisms in nucleotide pyrophosphatases. Here, we report that dUTPase, an essential nucleotide pyrophosphatase, uses a C-terminal P-loop-like sequence in a unique mechanism for ..
  87. ncbi Vacuolar H(+)-pyrophosphatase
    M Maeshima
    Laboratory of Biochemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
    Biochim Biophys Acta 1465:37-51. 2000
    ..In plant cells, H(+)-PPase coexists with H(+)-ATPase in a single vacuolar membrane. The physiological significance and the regulation of the gene expression of H(+)-PPase are also reviewed...
  88. ncbi The gene ygdP, associated with the invasiveness of Escherichia coli K1, designates a Nudix hydrolase, Orf176, active on adenosine (5')-pentaphospho-(5')-adenosine (Ap5A)
    M J Bessman
    Department of Biology and The McCollum Pratt Institute, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Biol Chem 276:37834-8. 2001
    ..near homogeneity and identified as a member of the Nudix hydrolase subfamily of dinucleoside oligophosphate pyrophosphatases. It catalyzes the hydrolysis of diadenosine tetra-, penta-, and hexa-phosphates with a preference for ..
  89. ncbi Crystal structure of Streptococcus mutans pyrophosphatase: a new fold for an old mechanism
    M C Merckel
    Institute of Biotechnology, University of Helsinki, Finland
    Structure 9:289-97. 2001
    ..Sm-PPase) is a member of a relatively uncommon but widely dispersed sequence family (family II) of inorganic pyrophosphatases. A structure will answer two main questions: is it structurally similar to the family I PPases, and is the ..
  90. ncbi Bacterial expression, folding, purification and characterization of soluble NTPDase5 (CD39L4) ecto-nucleotidase
    Deirdre M Murphy-Piedmonte
    Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, P O Box 670575, 231 Albert Sabin Way, Cincinnati, OH 45267 0575, USA
    Biochim Biophys Acta 1747:251-9. 2005
    ..Moreover, the substrate profile of bacterially expressed NTPDase5, as well as the C15S mutant, was determined to be similar to that of full-length, membrane-bound and soluble NTPDase5 expressed in mammalian COS cells...
  91. pmc PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification
    F Rutsch
    Department of Pediatrics, Municipal Children s Hospital, Dortmund, Germany
    Am J Pathol 158:543-54. 2001
    ....
  92. ncbi Chondrogenesis mediated by PPi depletion promotes spontaneous aortic calcification in NPP1-/- mice
    Kristen Johnson
    Rheumatology Medicine, Veterans Affairs Medical Center University of California at San Diego, School of Medicine, CA 92161, USA
    Arterioscler Thromb Vasc Biol 25:686-91. 2005
    ....
  93. ncbi Epistatic interactions between thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) variations determine 6-mercaptopurine toxicity in Indian children with acute lymphoblastic leukemia
    Patchva Dorababu
    Department of Medical Oncology, Nizam s Institute of Medical Sciences, Panjagutta, Hyderabad, Andhra Pradesh, India
    Eur J Clin Pharmacol 68:379-87. 2012
    ..To explore the role of genetic variants of thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) in 6-mercaptopurine (6-MP)-induced toxicity in Indian children with acute lymphoblastic leukemia (ALL)...
  94. pmc Complementation of Rickettsia rickettsii RelA/SpoT restores a nonlytic plaque phenotype
    Tina R Clark
    Host Parasite Interactions Section, Laboratory of Intracellular Parasites, NIAID, NIH, Rocky Mountain Laboratories, Hamilton, MT 59840, USA
    Infect Immun 79:1631-7. 2011
    ....
  95. ncbi Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn(2+)-dependent ADP-ribose/CDP-alcohol pyrophosphatase
    José Canales
    Grupo de Enzimologia, Departamento de Bioquimica y Biologia Molecular y Genetica, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain
    FEBS Lett 583:1593-8. 2009
    ..This is similar to the ADP-ribose/cADPR formation ratio by NADases. The product of cADPR phosphohydrolysis by ADPRibase-Mn was N(1)-(5-phosphoribosyl)-AMP, suggesting a novel route for cADPR turnover...
  96. ncbi New variants in the Enpp1 and Ptpn6 genes cause low BMD, crystal-related arthropathy, and vascular calcification
    Philip Babij
    Department of Metabolic Disorders, Amgen, Thousand Oaks, California 91320, USA
    J Bone Miner Res 24:1552-64. 2009
    ..This work confirms the utility of the chemical mutagenesis approach for identification of potential disease genes and confirms the role of Enpp1 and Ptpn6 in regulating mineralization and skeletal bone mass...
  97. ncbi A human endogenous retrovirus K dUTPase triggers a TH1, TH17 cytokine response: does it have a role in psoriasis?
    Maria Eugenia Ariza
    Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA
    J Invest Dermatol 131:2419-27. 2011
    ..These data support HERV-K dUTPase as a potential contributor to psoriasis pathophysiology...
  98. ncbi Cellular response to efficient dUTPase RNAi silencing in stable HeLa cell lines perturbs expression levels of genes involved in thymidylate metabolism
    Gabor Merenyi
    Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary
    Nucleosides Nucleotides Nucleic Acids 30:369-90. 2011
    ..Results indicate that RNAi silencing of dUTPase induces a complex cellular response wherein sensitivity towards fluoropyrimidines and gene expression levels of related enzymes are both modulated...
  99. pmc The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: evidence for interaction with obesity in diabetic patients
    Simonetta Bacci
    Unit of Endocrinology, IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo, Italy
    Diabetes 60:1000-7. 2011
    ..Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals...
  100. pmc The Nudix hydrolase CDP-chase, a CDP-choline pyrophosphatase, is an asymmetric dimer with two distinct enzymatic activities
    Krisna C Duong-Ly
    Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    J Bacteriol 193:3175-85. 2011
    ..CDP-Chase is the first identified member of a novel Nudix family in which structural asymmetry has a profound effect on the recognition of substrates...
  101. pmc Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients
    Alexander J Thompson
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27701, USA
    J Hepatol 56:313-9. 2012
    ..We performed a genome wide association study on a well-characterized genotype 1 HCV cohort to identify genetic determinants of peginterferon-α (pegIFN)-related thrombocytopenia, neutropenia, and leukopenia...

Research Grants51

  1. BIOENERGETICS AND PROTON PUMPS IN MALARIA PARASITES
    Akhil Vaidya; Fiscal Year: 2007
    ..contains two members (PfVP1 and PfVP2) of the plant-like energy- conserving, membrane-associated H*-pumping pyrophosphatases. The vacuolar pyrophosphatases (V-PPases) of plants couple the energy generated by hydrolysis of the ..
  2. Structure, Function and Mechanism of Nudix Hydrolases
    L Amzel; Fiscal Year: 2006
    ..family, which prevents mutations by eliminating the incorporation of 8-oxo-dGTP into DNA; b) the ADP-ribose pyrophosphatases, which have been associated with tellurite resistance in bacteria; c) the ApnA hydrolases, of which an Ap5A ..
  3. Novel Cap Analogs and Interactions with Target Proteins
    ROBERT RHOADS; Fiscal Year: 2005
    ..series of anti-reverse cap analogues, dinucleotide cap analogues intended to be resistant to degradation by pyrophosphatases, and capped trinucleotides...
  4. GLUTAMINE AMIDOTRANSFERASES AND PARTNER ENZYMES
    Janet Smith; Fiscal Year: 2007
    ..of both enzymes also represent homologous enzymes families, the phosphoribosyltransferases and the N-type ATP pyrophosphatases. Results from these first structures of amidotransferases have changed thinking about the enzyme family and ..
  5. PHOSPHOLIPID METABOLISM AND MEMBRANE FUNCTION
    GEORGE CARMAN; Fiscal Year: 2009
    ..Zinc transport function will be addressed with mutants defective in phospholipid synthesis, and with Zrtlp reconstituted into unilamellar vesicles with varying phospholipid composition. ..
  6. Computational Approach to Ligand Discovery for LPA GPCR and PPAR
    Abby L Parrill; Fiscal Year: 2010
    ..This research can therefore lead to new treatments for cardiovascular disease and cancer. ..
  7. ANK and Joint Ankylosis in Spondylitis
    Robert Terkeltaub; Fiscal Year: 2008
    ..These studies will identify novel targets for enthesopathic bone fusion in spondyloarthritis. ..
  8. ROLE OF DUTPASE EXPRESSION IN CANCER CHEMOTHERAPY
    Robert Ladner; Fiscal Year: 2003
    ....
  9. PTHRP 1 to 173 IN CHONDROCYTES
    Robert Terkeltaub; Fiscal Year: 2005
    ..Completion of these studies will indicate not only how PTHrP 1-173 can modulate OA, but also how functional properties of the PTHrP 1-173 C-terminal 140-173 domain can be harnessed to promote cartilage repair. ..
  10. dUTPase As A Prognostic Marker in Colon Cancer
    Robert Ladner; Fiscal Year: 2003
    ....
  11. Chondrocyte S100/Calgranulins and RAGE in Osteoarthritis
    Robert Terkeltaub; Fiscal Year: 2009
    ..Completion of the work will reveal new potential targets for therapeutic intervention in OA by disconnecting inflammation from deleterious alteration of chondrocyte differentiation and function. ..
  12. Expression and Structure of Soluble Human Nucleotidases
    TERENCE KIRLEY; Fiscal Year: 2006
    ..Second, it will demonstrate how two different protein primary structures are used to do the same enzymatic task, aiding in the design of more efficacious therapeutic soluble nucleotidases. ..
  13. ENZYMATIC SYNTHESIS OF NUCLEOTIDES AND DNA
    MAURICE BESSMAN; Fiscal Year: 2006
    ..New members of the gene family will be cloned, expressed, and characterized in respect to their particular biochemical reaction, their physiological functions, and their structure - function relationships. ..
  14. Phosphoinositide and Inositol Polyphosphate Probes
    Glenn Prestwich; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  15. Development of selenomethionine resistant yeast
    TERRI KINZY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  16. Fluorogenic Assays for Measuring the Activity of Ceramidase and Sphingomyelinase
    Colin Ferguson; Fiscal Year: 2008
    ..These assays will help to further basic research in this growing field and potentially be used for developing new drugs for diseases such as cancer, diabetes, and Alzheimer's disease. [unreadable] [unreadable] [unreadable]..
  17. REGULATION OF SECRETION FROM HUMAN BASOPHILS
    Donald MacGlashan; Fiscal Year: 2009
    ..A population of subjects will be examined for this relationship. ..
  18. POST-TRANSLATIONAL MECHANISMS IN URACIL-DNA REPAIR
    SALVATORE CARADONNA; Fiscal Year: 2004
    ..Our data indicate another level of regulation of this DNA repair enzyme. Since UDG1A is the first step in this DNA repair pathway, regulation of UDG1A activity will dictate control over the enitre pathway. ..
  19. Repair of Oxidatively Damaged Guanines
    A Lien Lu Chang; Fiscal Year: 2008
    ..We anticipate that these studies will advance our understanding of carcinogenesis process and form the background work for the development of new anti-cancer drugs. ..
  20. The contractile vacuole of Trypanosoma cruzi
    Roberto Docampo; Fiscal Year: 2010
    ..cruzi. Specific aim 2: To identify the molecular mechanism involved in the traffic T. cruzi aquaporin to the contractile vacuole complex and the role of aquaporin in regulatory volume decrease. ..
  21. Stress, the Immune System and Basal Cell Carcinoma
    Ronald Glaser; Fiscal Year: 2007
    ..2) We will determine if the relationships between depressive symptoms and severe life stressors and tumor immunoreactivity are more pronounced among older adults. ..
  22. Mechanisms of Nucleotide Release by Airway Epithelia
    Eduardo Lazarowski; Fiscal Year: 2006
    ..Delineation of nucleotide-releasing mechanisms will provide new possibilities to improve MCC function in chronic lung diseases characterized by mucin-obstructed and inflamed airways. [unreadable] [unreadable]..
  23. TRPM2 HTS Screening Assay Development(RMI)
    Andrew Scharenberg; Fiscal Year: 2005
    ..Using the 96 well plate format, we will also evaluate the overall method's properties and suitability for HTS using a library of compounds of known bioactivity. ..
  24. AUTOMATED DNA ANALYSIS SYSTEM
    TERRI KINZY; Fiscal Year: 2001
    ..Trained personnel of the core facility will run and maintain all equipment to ensure optimal quality and speed. These personnel will also provide ongoing technical support to all users of this equipment. ..
  25. ACIDOCALCISOMES IN TRYPANOSOMA CRUZI
    Roberto Docampo; Fiscal Year: 2002
    ..cruzi H+-pyrophosphatase; specific aim 3: investigation of the role of acidocalcisomes in intracellular Ca2+ and pH homeostasis. ..
  26. Carbonic Anhydrases in Obesity and Insulin Resistance
    JACK YOUNGREN; Fiscal Year: 2003
    ..These studies should provide important new data, therefore, on the CA family of enzymes, and their role in the insulin resistance. ..
  27. ACIDOCALCISOMES IN TRYPANOSOMA CRUZI
    Roberto Docampo; Fiscal Year: 2003
    ..cruzi, especially the role of acidocalcisomes and the contractile vacuole; Specific aim 2, Investigation of the role of acidocalcisome polyP in osmoregulation. ..
  28. ACTIVE SITE DETERMINATION OF THE E-TYPE ATPASES
    TERENCE KIRLEY; Fiscal Year: 2004
    ..abstract_text> ..
  29. Mineralization studies related to atherosclerosis
    HOWARD HSU; Fiscal Year: 2004
    ..abstract_text> ..
  30. ANALYSIS OF B-CELL RECEPTOR CALCIUM SIGNALING
    Andrew Scharenberg; Fiscal Year: 2004
    ..abstract_text> ..
  31. Liposome Overlays for Protein-Ligand Selectivity
    Colin Ferguson; Fiscal Year: 2004
    ..Finally we will develop PolyPIPosomes TM and PIPosomes TM research products and establish collaborations for beta-testing products to facilitate their introduction to the market. ..
  32. Pathway of Spontaneous Mutagenesis in Escherichia coli
    Robert Fowler; Fiscal Year: 2004
    ..Humans possess a number of these specialized DNA polymerases whose activities may be responsible for a significant portion of the human mutational load. ..
  33. Structure of Eukaryotic Translation Elongation Factor 1
    TERRI KINZY; Fiscal Year: 2004
    ..With S. cerevisiae, the structural information obtained on eEF1A can be utilized for molecular genetic analysis of the critical residues for function and regulation. ..
  34. Crosslinkable Hydrogels for Tympanic Membrane Repair
    Glenn Prestwich; Fiscal Year: 2004
    ..Third, we will evaluate the biocompability and otocompability of each gel in vivo by evaluating recovery of auditory function and middle ear histology. ..
  35. A Bioinformatic Approach to Inferring Protein Contacts
    MARCELLA MCCLURE; Fiscal Year: 2005
    ..Several experimental laboratories have agreed to test the residue contact predictions resulting from these studies for Ebola, VSV and measles. ..
  36. MINERALIZATION STUDIES RELATED TO ORAL BIOLOGY
    HARRISON ANDERSON; Fiscal Year: 2005
    ..New knowledge of matrix vesicle calcification can be applied to a broad range of topics including specific diseases in which abnormal calcification occurs. ..
  37. Autocrine control of neutrophil chemotaxis
    Wolfgang G Junger; Fiscal Year: 2010
    ..abstract_text> ..
  38. Targeted gene repair of primary immune deficiencies
    Andrew Scharenberg; Fiscal Year: 2006
    ..Overall, the work proposed here will build a foundation of materials and experience for the development of LHE's as general tools for targeted gene therapy of human primary immune deficiencies. ..
  39. Molecular mechanisms of vertebrate Mg2+ homeostasis
    Andrew Scharenberg; Fiscal Year: 2009
    ..Together, the proposed studies will generate a foundation of knowledge on the molecular mechanisms of Mg uptake and their integration with mechanisms which regulate cell growth and proliferation. ..
  40. MOLECULAR BASIS OF CALCIUM PYROPHOSPHATE DEPOSITION
    Ikuko Masuda; Fiscal Year: 2002
    ..It is hoped that these studies will lead to therapies to reduce ePPi accumulation and reduce subsequent cartilage degeneration. ..
  41. NMR STUDIES OF ENZYMES/METAL SUBSTRATE INTERACTIONS
    ALBERT MILDVAN; Fiscal Year: 2004
    ..The purpose of studying multiple enzymes which catalyze reactions of the same class is to elucidate general principles of enzyme chemistry and to develop new approaches to enzyme structure and mechanism. ..
  42. MECHANISTIC STUDIES OF DNA MISMATCH REPAIR
    A Lien Lu Chang; Fiscal Year: 2006
    ..Particularly, alterations in protein-protein interactions under oxidative stress will be investigated. These studies should advance our understanding of the role of DNA repair in genome stability and tumor susceptibility. ..
  43. Exercise Training in Insulin Resistant Non-Diabetics
    Ira Goldfine; Fiscal Year: 2006
    ..abstract_text> ..
  44. Thiol-Reactive Crosslinkers for Biomaterials
    Glenn Prestwich; Fiscal Year: 2004
    ..Fourth, these new materials will be evaluated for cytocompatibility and cell growth in vitro with murine fibroblasts. Finally, selected materials will be seeded with fibroblasts and injected into nude mice for in vivo tissue generation. ..
  45. Diabesity Gene Discovery at Chromosome 6q23
    Christopher Jenkinson; Fiscal Year: 2008
    ..abstract_text> ..
  46. PC-1 Insulin Receptor Signaling
    Ira Goldfine; Fiscal Year: 2009
    ..We will determine therefore whether PC-1 overexpression in fibroblast is caused by transcriptional and/or post-transcriptional mechanisms. ..
  47. SQUALENE AND OXIDOSQUALENE CYCLASES
    Glenn Prestwich; Fiscal Year: 2002
    ....
  48. DEVELOPMENT OF A LIVE ATTENUATED HSV-2 VACCINE
    Mark Prichard; Fiscal Year: 2002
    ..In addition further in vitro characterization will enable high quality clinical trial material to be produced for IND enabling primate studies and early Phase I human trials. PROPOSED COMMERCIAL APPLICATION: Not Available ..