n glycosyl hydrolases

Summary

Summary: A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.

Top Publications

  1. ncbi Role of electrophilic and general base catalysis in the mechanism of Escherichia coli uracil DNA glycosylase
    A C Drohat
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, National Institute for Standards and Technology, Rockville, Maryland 20850, USA
    Biochemistry 38:11866-75. 1999
  2. ncbi Heteronuclear NMR and crystallographic studies of wild-type and H187Q Escherichia coli uracil DNA glycosylase: electrophilic catalysis of uracil expulsion by a neutral histidine 187
    A C Drohat
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, National Institute for Standards and Technology, Rockville, Maryland 20850, USA
    Biochemistry 38:11876-86. 1999
  3. ncbi Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1 methyltransferase and DME glycosylase
    Wenyan Xiao
    Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA 94720, USA
    Dev Cell 5:891-901. 2003
  4. ncbi Pokeweed antiviral protein inhibits brome mosaic virus replication in plant cells
    Daniel Picard
    Department of Biology, York University, Toronto, Ontario, Canada
    J Biol Chem 280:20069-75. 2005
  5. pmc Glucosinolate metabolites required for an Arabidopsis innate immune response
    Nicole K Clay
    Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 323:95-101. 2009
  6. pmc Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein
    J P McGoldrick
    Department of Biological Chemistry, School of Medicine, University of Maryland at Baltimore, 21201
    Mol Cell Biol 15:989-96. 1995
  7. ncbi Catalysis by nucleoside hydrolases
    Wim Versées
    Department of Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel, Belgium
    Curr Opin Struct Biol 13:731-8. 2003
  8. ncbi Identification of a new uracil-DNA glycosylase family by expression cloning using synthetic inhibitors
    K A Haushalter
    Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA
    Curr Biol 9:174-85. 1999
  9. ncbi DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in arabidopsis
    Yeonhee Choi
    Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 110:33-42. 2002
  10. pmc DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation
    Mary Gehring
    Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 124:495-506. 2006

Research Grants

Detail Information

Publications190 found, 100 shown here

  1. ncbi Role of electrophilic and general base catalysis in the mechanism of Escherichia coli uracil DNA glycosylase
    A C Drohat
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, National Institute for Standards and Technology, Rockville, Maryland 20850, USA
    Biochemistry 38:11866-75. 1999
    ..In the following paper of this issue we establish by crystallography and heteronuclear NMR spectroscopy that the imidazole of His187 is neutral during the catalytic cycle of UDG...
  2. ncbi Heteronuclear NMR and crystallographic studies of wild-type and H187Q Escherichia coli uracil DNA glycosylase: electrophilic catalysis of uracil expulsion by a neutral histidine 187
    A C Drohat
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, National Institute for Standards and Technology, Rockville, Maryland 20850, USA
    Biochemistry 38:11876-86. 1999
    ..Rather, we propose a concerted mechanism involving general base catalysis by Asp64 and electrophilic stabilization of the developing enolate on uracil O2 by a neutral His187...
  3. ncbi Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1 methyltransferase and DME glycosylase
    Wenyan Xiao
    Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA 94720, USA
    Dev Cell 5:891-901. 2003
    ..Our data suggest that imprinting is controlled in the female gametophyte by antagonism between the two DNA-modifying enzymes, MET1 methyltransferase and DME DNA glycosylase...
  4. ncbi Pokeweed antiviral protein inhibits brome mosaic virus replication in plant cells
    Daniel Picard
    Department of Biology, York University, Toronto, Ontario, Canada
    J Biol Chem 280:20069-75. 2005
    ..These novel activities are distinct from the PAP-induced reduction of viral RNA translation and represent new targets for the inhibition of viral infection...
  5. pmc Glucosinolate metabolites required for an Arabidopsis innate immune response
    Nicole K Clay
    Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 323:95-101. 2009
    ..Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens...
  6. pmc Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein
    J P McGoldrick
    Department of Biological Chemistry, School of Medicine, University of Maryland at Baltimore, 21201
    Mol Cell Biol 15:989-96. 1995
    ..The eukaryotic MYH may be involved in the major repair of both replication errors and oxidative damage to DNA, the same functions as those of the E. coli MutY protein...
  7. ncbi Catalysis by nucleoside hydrolases
    Wim Versées
    Department of Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel, Belgium
    Curr Opin Struct Biol 13:731-8. 2003
    ..However, the mechanisms underlying leaving group activation are still the subject of debate for the nucleoside hydrolases...
  8. ncbi Identification of a new uracil-DNA glycosylase family by expression cloning using synthetic inhibitors
    K A Haushalter
    Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA
    Curr Biol 9:174-85. 1999
    ..DNA glycosylases protect the integrity of the genome by catalyzing the first step in the base excision-repair of lesions in DNA...
  9. ncbi DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in arabidopsis
    Yeonhee Choi
    Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 110:33-42. 2002
    ..In leaf, ectopic DME expression induces MEA and nicks the MEA promoter. Thus, a DNA glycosylase activates maternal expression of an imprinted gene in the central cell...
  10. pmc DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation
    Mary Gehring
    Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 124:495-506. 2006
    ..Thus, DME establishes MEA imprinting by removing 5-methylcytosine to activate the maternal allele. MEA imprinting is subsequently maintained in the endosperm by maternal MEA silencing the paternal allele...
  11. ncbi Binding interactions between the active center cleft of recombinant pokeweed antiviral protein and the alpha-sarcin/ricin stem loop of ribosomal RNA
    F Rajamohan
    Biotherapy Program, Parker Hughes Cancer Center, and the Departments of Protein Engineering, Structural Biology, and Virology, Parker Hughes Institute, St Paul, Minnesota 55113, USA
    J Biol Chem 276:24075-81. 2001
    ....
  12. ncbi The RihA, RihB, and RihC ribonucleoside hydrolases of Escherichia coli. Substrate specificity, gene expression, and regulation
    C Petersen
    Department of Biological Chemistry, Institute of Molecular Biology, University of Copenhagen, Sølvgade 83H, DK1307 Copenhagen K, Denmark
    J Biol Chem 276:884-94. 2001
    ..Furthermore, enzyme assays and lacZ gene fusion analysis indicated that rihB was essentially silent unless activated by mutation, whereas rihA and rihC were poorly expressed in glucose medium due to catabolite repression...
  13. pmc DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases
    Teresa Morales-Ruiz
    Departamento de Genetica, Universidad de Cordoba, 14071 Cordoba, Spain
    Proc Natl Acad Sci U S A 103:6853-8. 2006
    ..These findings suggest that a function of ROS1 and DME is to initiate erasure of 5-meC through a base excision repair process and provide strong biochemical evidence for the existence of an active DNA demethylation pathway in plants...
  14. ncbi Active center cleft residues of pokeweed antiviral protein mediate its high-affinity binding to the ribosomal protein L3
    F Rajamohan
    Biotherapy Program, Parker Hughes Cancer Center, Parker Hughes Institute, St Paul, Minnesota 55113, USA
    Biochemistry 40:9104-14. 2001
    ..The experimental findings presented in this report provide unprecedented evidence that the active center cleft of PAP is important for its in vitro binding to ribosomes via the L3 protein...
  15. ncbi One-way control of FWA imprinting in Arabidopsis endosperm by DNA methylation
    Tetsu Kinoshita
    Integrated Genetics, National Institute of Genetics, Mishima 411 8540, Japan
    Science 303:521-3. 2004
    ..Because endosperm does not contribute to the next generation, the activated FWA gene need not be silenced again. Double fertilization enables plants to use such "one-way" control of imprinting and DNA methylation in endosperm...
  16. pmc Maintenance of DNA methylation during the Arabidopsis life cycle is essential for parental imprinting
    Pauline E Jullien
    Chromatin and Reproduction Group, Temasek Lifesciences Laboratory, National University of Singapore, Singapore 117604, Republic of Singapore
    Plant Cell 18:1360-72. 2006
    ..We propose that imprinting has evolved under constraints linked to the evolution of plant reproduction and not by the selection of a specific molecular mechanism...
  17. ncbi A new class of uracil-DNA glycosylases related to human thymine-DNA glycosylase
    P Gallinari
    Istituto di Richerche di Biologia Molecolare P Angeletti, Pomezia, Italy
    Nature 383:735-8. 1996
    ....
  18. pmc Excision of cytosine and thymine from DNA by mutants of human uracil-DNA glycosylase
    B Kavli
    UNIGEN Center for Molecular Biology, The Norwegian University of Science and Technology, Trondheim, Norway
    EMBO J 15:3442-7. 1996
    ..Three of the four new pyrimidine-DNA glycosylases resulted from single nucleotide substitutions, events that may also happen in vivo...
  19. ncbi Pre- and postinvasion defenses both contribute to nonhost resistance in Arabidopsis
    Volker Lipka
    Department of Plant Microbe Interactions, Max Planck Institute for Plant Breeding Research, Carl von Linne Weg 10, D 50829 Köln, Germany
    Science 310:1180-3. 2005
    ..Concurrent impairment of pre- and postinvasion resistance renders Arabidopsis a host for both nonadapted fungi...
  20. ncbi Crystal structure to 1.7 a of the Escherichia coli pyrimidine nucleoside hydrolase YeiK, a novel candidate for cancer gene therapy
    Barbara Giabbai
    Biocrystallography Unit, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, I 20132 Milan, Italy
    Structure 12:739-49. 2004
    ..The high catalytic efficiency of YeiK toward 5-fluorouridine could be exploited for suicide gene therapy in cancer treatment...
  21. pmc Remote mutations and active site dynamics correlate with catalytic properties of purine nucleoside phosphorylase
    Suwipa Saen-oon
    Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biophys J 94:4078-88. 2008
    ..That motion and catalysis are enhanced by mutations remote from the catalytic site implicates dynamic coupling through the protein architecture as a component of catalysis in hPNP...
  22. pmc Cloning and expression in Escherichia coli of the OGG1 gene of Saccharomyces cerevisiae, which codes for a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine
    P A Van Der Kemp
    Unité de Recherche Associée 147 Centre National de la Recherche Scientifique, Villejuif, France
    Proc Natl Acad Sci U S A 93:5197-202. 1996
    ..The mechanism of strand cleavage by Ogg1 protein is probably due to the excision of 8-OxoG followed by a beta-elimination at the resulting apurinic/apyrimidinic site...
  23. pmc Transition-state analysis of S. pneumoniae 5'-methylthioadenosine nucleosidase
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 129:2783-95. 2007
    ..pneumoniae MTAN. This feature differentiates the S. pneumoniae and E. coli transition states and explains the 10(3)-fold decrease in the catalytic efficiency of S. pneumoniae MTAN relative to that from E. coli...
  24. ncbi Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions
    T E Barrett
    Department of Biochemistry and Molecular Biology, University College London, United Kingdom
    Cell 92:117-29. 1998
    ..Details of the MUG structure explain its thymine DNA-glycosylase activity and the specificity for G:U/T mispairs, which derives from direct recognition of guanine on the complementary strand...
  25. ncbi Structural rationale for the affinity of pico- and femtomolar transition state analogues of Escherichia coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase
    Jeffrey E Lee
    Structural Biology and Biochemistry, Research Institute, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    J Biol Chem 280:18274-82. 2005
    ..Distance analysis of the nucleophile and leaving group show that MT-ImmA is a mimic of an early transition state, while MT-DADMe-ImmA is a better mimic of the highly dissociated transition state of E. coli MTAN...
  26. ncbi Transition state structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Escherichia coli and its similarity to transition state analogues
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 44:11647-59. 2005
    ..Transition state analogues that resemble this transition state structure are powerful inhibitors, and their molecular electrostatic potential maps closely resemble that of the transition state...
  27. pmc Transition-state structure of neisseria meningitides 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 129:13831-3. 2007
  28. pmc X-ray crystallographic analysis of the structural basis for the interaction of pokeweed antiviral protein with guanine residues of ribosomal RNA
    I V Kurinov
    Department of Structural Biology, Hughes Institute, Roseville, Minnesota 55113, USA
    Protein Sci 8:2399-405. 1999
    ..This prediction was experimentally confirmed, since a guanine base was visible in the active site pocket of the crystal structure of the PAP-guanine complex...
  29. ncbi The salivary purine nucleosidase of the mosquito, Aedes aegypti
    Jose M C Ribeiro
    Section of Medical Entomology, Laboratory of Parasitic Diseases, Building 4, Room 126, 4 Center Drive, MSC 0425, NIH, MD 20892 0425, Bethesda, USA
    Insect Biochem Mol Biol 33:13-22. 2003
    ..aegypti salivary gland homogenates (SGH) have very low purine nucleosidase activity, suggesting that the enzyme plays a role in mosquito blood feeding. A novel isocratic HPLC method to separate nucleosides and their bases is described...
  30. ncbi The URH1 uridine ribohydrolase of Saccharomyces cerevisiae
    Jean Emmanuel Kurtz
    Laboratoire de Genetique, UPR 9003 du CNRS, IRCAD, Strasbourg, France
    Curr Genet 41:132-41. 2002
    ..These results allow us to speculate that the structure and catalytic mechanism of Urh1p are similar to the inosine/uridine nucleoside hydrolase from C. fasciculata...
  31. ncbi X-ray crystallographic analysis of pokeweed antiviral protein-II after reductive methylation of lysine residues
    I V Kurinov
    Department of Structural Biology, Parker Hughes Institute, Roseville, Minnesota 55113, USA
    Biochem Biophys Res Commun 275:549-52. 2000
    ..51 A, c = 79.05 A, were obtained using 1.8 M Na/K phosphate as the precipitant. These crystals contained one enzyme molecule per asymmetric unit and diffracted up to 2.4 A, when exposed to a synchroton source...
  32. ncbi Structural basis for substrate specificity in group I nucleoside hydrolases
    Elena Iovane
    Biocrystallography Unit, DIBIT San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy
    Biochemistry 47:4418-26. 2008
    ..Our study provides for the first time direct evidence that distinct subsets of amino acid residues are involved in the hydrolysis of purine or pyrimidine nucleosides in group I NHs...
  33. pmc Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA
    S S Parikh
    The Skaggs Institute for Chemical Biology, Department of Molecular Biology, MB 4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 1027, USA
    EMBO J 17:5214-26. 1998
    ..Thus, AP site binding may couple damage-specific and damage-general steps of BER without requiring direct protein-protein interactions...
  34. pmc Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage
    M M Slupska
    Department of Microbiology and Molecular Genetics, University of California, Los Angeles, California 90024, USA
    J Bacteriol 178:3885-92. 1996
    ..The human mutY gene maps on the short arm of chromosome 1, between p32.1 and p34.3...
  35. ncbi Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis
    C D Mol
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037
    Cell 80:869-78. 1995
    ..Specific binding of uracil flipped out from a DNA duplex provides a structural mechanism for damaged base recognition...
  36. ncbi Cloning, purification, crystallization and X-ray analysis of the Escherichia coli pyrimidine nucleoside hydrolase YeiK
    Barbara Giabbai
    DIBIT Scientific Institute S Raffaele, I 20132 Milan, Italy
    Acta Crystallogr D Biol Crystallogr 60:524-7. 2004
    ..Crystals of YeiK diffract X-rays to a resolution of 1.7 A and belong to the triclinic crystal system in space group P1, with unit-cell parameters a = 44.81, b = 85.71, c = 90.68 A, alpha = 112.95, beta = 101.95, gamma = 85.92 degrees...
  37. ncbi New insights into the mechanism of nucleoside hydrolases from the crystal structure of the Escherichia coli YbeK protein bound to the reaction product
    Laura Muzzolini
    Biocrystallography Unit, DIBIT Scientific Institute S Raffaele, Via Olgettina 58, 20132 Milan, Italy
    Biochemistry 45:773-82. 2006
    ....
  38. ncbi Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax
    Wim Versées
    Department of Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B 1640 Sint Genesius Rode, Belgium
    J Biol Chem 277:15938-46. 2002
    ..The parallel aromatic stacking seems to provide the most likely alternative mechanism for leaving group activation...
  39. ncbi The role of a purine-specific nucleoside hydrolase in spore germination of Bacillus thuringiensis
    Liang Liang
    State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China
    Microbiology 154:1333-40. 2008
    ..89+/-0.23x10(-2) micromol min(-1) (mg dry wt)(-1). These results indicate that IunH is important in moderating inosine- or adenosine-induced germination of Bacillus thuringiensis spores...
  40. pmc Analysis of rice glycosyl hydrolase family 1 and expression of Os4bglu12 beta-glucosidase
    Rodjana Opassiri
    Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
    BMC Plant Biol 6:33. 2006
    ....
  41. pmc Pokeweed antiviral protein binds to the cap structure of eukaryotic mRNA and depurinates the mRNA downstream of the cap
    Katalin A Hudak
    Biotechnology Center for Agriculture and Environment, Department of Plant Biology and Pathology, Cook College, Rutgers University, New Brunswick, New Jersey 08903, USA
    RNA 8:1148-59. 2002
    ..These findings may have implications for understanding PAP activity in vivo...
  42. ncbi Multiple transients in the pre-steady-state of nucleoside hydrolase reveal complex substrate binding, product base release, and two apparent rates of chemistry
    An Vandemeulebroucke
    Department of Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel, Belgium
    Biochemistry 45:9307-18. 2006
    ..base dead-end complex, and not the rapid equilibrium random uni-bi mechanism proposed for other NHs. Two applicable kinetic models are presented and their implications for future mechanistic studies discussed...
  43. ncbi Exploring nucleoside hydrolase catalysis in silico: molecular dynamics study of enzyme-bound substrate and transition state
    Devleena Mazumder
    Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, USA
    J Am Chem Soc 124:14591-600. 2002
    ..S and E.S is observed. The relationship of this anticorrelated motion to mechanism, if any, deserves further exploration, perhaps the formation of a near attack conformation...
  44. pmc Structure-based design and engineering of a nontoxic recombinant pokeweed antiviral protein with potent anti-human immunodeficiency virus activity
    Fatih M Uckun
    Biotherapy Program, Parker Hughes Cancer Center, St Paul, Minnesota 55113, USA
    Antimicrob Agents Chemother 47:1052-61. 2003
    ....
  45. ncbi Kinetic isotope effects of nucleoside hydrolase from Escherichia coli
    Cindy Hunt
    Department of Chemistry, Middle Tennessee State University, Box 68, Murfreesboro, TN 37132, USA
    Biochim Biophys Acta 1751:140-9. 2005
    ..The proposed transition state for the prokaryotic E. coli nucleoside hydrolase is compared to that of a similar enzyme isolated from Crithidia fasciculata (C. fasciculata)...
  46. ncbi Femtomolar transition state analogue inhibitors of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Escherichia coli
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 280:18265-73. 2005
    ..The accompanying article reports crystal structures of MTAN with these analogues...
  47. pmc Structure and inhibition of a quorum sensing target from Streptococcus pneumoniae
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 45:12929-41. 2006
    ..coli enzyme. Catalytic site efficiency is primarily responsible for this difference since k(cat)/K(m) for S. pneumoniae MTAN is decreased 845-fold relative to that of E. coli MTAN...
  48. ncbi Expression of biologically active recombinant pokeweed antiviral protein in methylotrophic yeast Pichia pastoris
    F Rajamohan
    Biotherapy Program, Hughes Institute, Roseville, Minnesota 55113, USA
    Protein Expr Purif 18:193-201. 2000
    ..americana. To our knowledge, this is the first large-scale expression and purification of soluble and biologically active recombinant mature PAP from yeast...
  49. ncbi Three-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata
    M Degano
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 35:5971-81. 1996
    ..L., Horenstein, B. A., & Kline, P. C. (1994) J. Biol. Chem. 269, 18259-18262]...
  50. pmc TXU (anti-CD7)-pokeweed antiviral protein as a potent inhibitor of human immunodeficiency virus
    F M Uckun
    Wayne Hughes Institute, St Paul, Minnesota 55113, USA
    Antimicrob Agents Chemother 42:383-8. 1998
    ..Furthermore, plasma samples from TXU-PAP-treated cynomolgus monkeys showed potent anti-HIV-1 activity in vitro...
  51. ncbi Thermostable uracil-DNA glycosylase from Thermotoga maritima a member of a novel class of DNA repair enzymes
    M Sandigursky
    Departments of Radiology and Radiation Oncology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Curr Biol 9:531-4. 1999
    ..These findings suggest that the T. maritima UDG is a member of a new class of DNA repair enzymes...
  52. ncbi Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+
    Peter Belenky
    Departments of Genetics and Biochemistry and the Norris Cotton Cancer Center, Dartmouth Medical School, Rubin 733 HB7937, Lebanon, NH 03756, USA
    Cell 129:473-84. 2007
    ..Thus, like calorie restriction in the mouse, nicotinamide riboside elevates NAD(+) and increases Sir2 function...
  53. ncbi Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor
    M Degano
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 37:6277-85. 1998
    ..The mechanism is ribooxocarbenium stabilization with weak leaving group activation and is a departure from glucohydrolases which use paired carboxylates to achieve the transition state...
  54. pmc 3,N4-ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase
    M Saparbaev
    Groupe Reparation des lesions Radio et Chimio Induites, UMR 1772, Centre National de la Recherche Scientifique, Institut Gustave Roussy, 94805 Villejuif Cedex, France
    Proc Natl Acad Sci U S A 95:8508-13. 1998
    ..coli dsUDG and hTDG proteins in vitro suggests that these enzymes may be responsible for the repair of this mutagenic lesion in vivo and be important contributors to genetic stability...
  55. pmc Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein
    A Erice
    Department of Laboratory Medicine, University of Minnesota Health Sciences Center, Minneapolis 55455, USA
    Antimicrob Agents Chemother 37:835-8. 1993
    ....
  56. ncbi Pokeweed antiviral protein: a potential nonspermicidal prophylactic antiviral agent
    O J D'Cruz
    Department of Reproductive Biology, Parker Hughes Institute, St Paul, Minnesota 55113, USA
    Fertil Steril 75:106-14. 2001
    ..To investigate the effects of pokeweed antiviral protein (PAP), a 29-kDa anti-human immunodeficiency virus (HIV) protein purified from the leaves of Phytolacca americana, on human sperm function...
  57. ncbi High resolution X-ray structure of potent anti-HIV pokeweed antiviral protein-III
    Igor V Kurinov
    The Biotherapy and Drug Discovery Program, Parker Hughes Cancer Center, 2699 Patton Road, St Paul, MN 55113, USA
    Biochem Pharmacol 65:1709-17. 2003
    ..In accordance with the predictions of the modeling studies, PAP-III was more potent than PAP-I in depurinating HIV-1 RNA...
  58. pmc C-terminal deletion mutant of pokeweed antiviral protein inhibits viral infection but does not depurinate host ribosomes
    N E Tumer
    Agricultural Biotechnology Center and Department of Plant Pathology, Rutgers University, Cook College, New Brunswick, NJ 08903 0231, USA
    Proc Natl Acad Sci U S A 94:3866-71. 1997
    ..An intact C terminus is also required for toxicity and depurination of tobacco ribosomes in vivo, but not for antiviral activity, suggesting that antiviral activity of PAP can be dissociated from its toxicity...
  59. ncbi The C-terminal domain of MutY glycosylase determines the 7,8-dihydro-8-oxo-guanine specificity and is crucial for mutation avoidance
    X Li
    Department of Biochemistry and Molecular Biology, University of Maryland at Baltimore, Baltimore, Maryland 21201, USA
    J Biol Chem 275:8448-55. 2000
    ..These findings strongly suggest that the C-terminal domain of MutY determines the 8-oxoG specificity and is crucial for mutation avoidance by oxidative damage...
  60. ncbi Opposite base specificity in excision of pyrimidine ring-opened 1,N6-ethenoadenine by thymine glycol-DNA-glycosylases
    Monika Bajek
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02 106, Warsaw, Poland
    DNA Repair (Amst) 1:251-7. 2002
    ..Thus, when paired with A, an epsilon A derivative might be more persistent than when paired with other bases and give rise to AT-->TA transversions...
  61. ncbi Mutagenic target for hydroxyl radicals generated in Escherichia coli mutant deficient in Mn- and Fe- superoxide dismutases and Fur, a repressor for iron-uptake systems
    Tatsuo Nunoshiba
    Department of Biomolecular Science, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980 8577, Japan
    DNA Repair (Amst) 1:411-418. 2002
    ..coli was similar to that in sodAB fur strain. These results suggested that the targets contributing to oxidative mutagenesis in sodAB fur strain are nucleotides such as dGTP and dATP, rather than DNA...
  62. ncbi Cytotoxicity and mutagenesis induced by singlet oxygen in wild type and DNA repair deficient Escherichia coli strains
    Ana Karina Dias Cavalcante
    Departamento de Biologia Celular e Genetica, Centro de Biociencias, Universidade Federal do Rio Grande do Norte, Natal CEP 59072970, RN, Brazil
    DNA Repair (Amst) 1:1051-6. 2002
    ..As (1)O(2) is highly reactive, its interaction with cell membranes may generate secondary products that could react with DNA, leading to mutagenic lesions...
  63. pmc Age-dependent deficiency in import of mitochondrial DNA glycosylases required for repair of oxidatively damaged bases
    Bartosz Szczesny
    Sealy Center for Molecular Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
    Proc Natl Acad Sci U S A 100:10670-5. 2003
    ..These results indicate an age-dependent decline in the mitochondrial import of proteins needed for DNA repair and possibly for other functions...
  64. ncbi MutY DNA glycosylase: base release and intermediate complex formation
    D O Zharkov
    Department of Pharmacological Sciences, State University of New York at Stony Brook 11794l 8651, USA
    Biochemistry 37:12384-94. 1998
    ..The MutY-DNA intermediate complex is highly stable and hinders access by Fpg to DNA, thereby avoiding a double-strand break. Cross-linking of MutY to DNA may play an important role in the regulation of base excision repair...
  65. ncbi Activity of Escherichia coli DNA-glycosylases on DNA damaged by methylating and ethylating agents and influence of 3-substituted adenine derivatives
    B Tudek
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw
    Mutat Res 407:169-76. 1998
    ..Taken together, these results suggest that hydrophobic interactions are involved in the mechanism of inhibition and/or recognition and excision of alkylated purines by TagA protein...
  66. ncbi Base excision repair capacity in mitochondria and nuclei: tissue-specific variations
    Bensu Karahalil
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
    FASEB J 16:1895-902. 2002
    ..There was no correlation between glycosylase activities in the mitochondrial extracts and COX activity, suggesting that DNA repair enzymes may be regulated by a mechanism different from this mitochondrial enzyme...
  67. ncbi Clustered DNA damage, influence on damage excision by XRS5 nuclear extracts and Escherichia coli Nth and Fpg proteins
    M H David-Cordonnier
    Medical Research Council, Radiation and Genome Stability Unit, Harwell, Didcot, Oxon, OX11 0RD, United Kingdom
    J Biol Chem 275:11865-73. 2000
    ..Therefore, this large inhibition of the excision of DHT by the presence of an opposite AP site may minimize the formation of double-strand breaks in the processing of DNA clustered damages...
  68. pmc Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA
    Ingrid Morland
    Department of Molecular Biology, Institute of Medical Microbiology, University of Oslo, Rikshospitalet, 0027 Oslo, Norway
    Nucleic Acids Res 30:4926-36. 2002
    ..It thus appears that hFPG1 has properties similar to mammalian OGG1 in preventing mutations arising from misincorporation of A across 8-oxoG and could function as a back-up repair activity for OGG1 in ogg1(-/-) mice...
  69. ncbi Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways
    Robert G Fowler
    Department of Biological Sciences, San Jose State University, San Jose, CA 95192, USA
    DNA Repair (Amst) 2:159-73. 2003
    ..T-->C.G transversions in the mutT(+) background, suggesting that, even in the presence of functional MutT protein, A.T-->C.G transversions may still result from 8-oxodGTP misincorporation...
  70. ncbi Escherichia coli MutY and Fpg utilize a processive mechanism for target location
    Anthony W Francis
    Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, Utah 84112, USA
    Biochemistry 42:801-10. 2003
    ..A- and G.A-containing substrates. This suggests that the C-terminal domain of MutY plays an important role in the mechanism by which the enzyme detects OG.A base pairs in DNA...
  71. pmc A novel role for Escherichia coli endonuclease VIII in prevention of spontaneous G-->T transversions
    J O Blaisdell
    Department of Microbiology, The Markey Center for Molecular Genetics, The University of Vermont, Burlington, Vermont 05405 0068, USA
    J Bacteriol 181:6396-402. 1999
    ..This was confirmed by showing that, indeed, endo VIII can recognize 8-oxoG in vitro...
  72. ncbi Repair of DNA containing Fapy.dG and its beta-C-nucleoside analogue by formamidopyrimidine DNA glycosylase and MutY
    Carissa J Wiederholt
    Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA
    Biochemistry 42:9755-60. 2003
    ..The similar effects of Fapy.dG and 8-oxodG on DNA polymerase and repair enzymes in vitro raise the question as to whether Fapy.dG elicits similar effects in vivo...
  73. ncbi Base excision repair activities required for yeast to attain a full chronological life span
    Morag J Maclean
    Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC 1E 6BT, UK
    Aging Cell 2:93-104. 2003
    ..They also reveal an appreciable overlap in the G0 maintenance functions of the different BER DNA glycosylases and AP endonucleases...
  74. ncbi Probing the requirements for recognition and catalysis in Fpg and MutY with nonpolar adenine isosteres
    Anthony W Francis
    Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah, 84112, USA
    J Am Chem Soc 125:16235-42. 2003
    ..Taken together, these results point to the importance of both N7 and N3 in the mechanism of adenine excision catalyzed by MutY...
  75. pmc Stereoselective excision of thymine glycol from oxidatively damaged DNA
    Holly Miller
    Laboratory of Chemical Biology, State University of New York, Stony Brook, NY, USA
    Nucleic Acids Res 32:338-45. 2004
    ..When DNA glycosylases occur as complementary pairs, failure of one or both enzymes to excise their cognate Tg stereoisomer from oxidatively damaged DNA could have deleterious consequences for the cell...
  76. ncbi Energetics of lesion recognition by a DNA repair protein: thermodynamic characterization of formamidopyrimidine-glycosylase (Fpg) interactions with damaged DNA duplexes
    Conceição A S A Minetti
    Department of Chemistry and Chemical Biology, Rutgers University, Wright Chemistry Bldg, 610 Taylor Road Rm 0156, Piscataway, NJ 08854 8087, USA
    J Mol Biol 328:1047-60. 2003
    ....
  77. pmc Excision of oxidatively damaged DNA bases by the human alpha-hOgg1 protein and the polymorphic alpha-hOgg1(Ser326Cys) protein which is frequently found in human populations
    C Dherin
    CEA, DSV, DRR, UMR217 CNRS CEA, Radiobiologie Moléculaire et Cellulaire, Fontenay aux Roses, France
    Nucleic Acids Res 27:4001-7. 1999
    ..Furthermore, both proteins efficiently complement the mutator phenotype of the fpg mutY mutant of Escherichia coli...
  78. pmc Differential subcellular localization of human MutY homolog (hMYH) and the functional activity of adenine:8-oxoguanine DNA glycosylase
    M Takao
    Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 4 1 Seiryo machi, Aoba ku, Sendai 980 8578, Japan
    Nucleic Acids Res 27:3638-44. 1999
    ..These results represent the first demonstration of the function of the hMYH gene product which is differentially transported into the nucleus or the mitochondria by alternative splicing..
  79. ncbi Escherichia coli uracil- and ethenocytosine-initiated base excision DNA repair: rate-limiting step and patch size distribution
    Jung Suk Sung
    Departments of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331 7301, USA
    Biochemistry 42:4613-25. 2003
    ..This BER process was dependent upon DNA polymerase I since very-long patch BER was inhibited by DNA polymerase I antibody and addition of excess DNA polymerase I reversed this inhibition...
  80. ncbi DNA damage and repair system in spinal cord ischemia
    Ruxian Lin
    Cardiothoracic Renal Research Program, Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
    J Vasc Surg 37:847-58. 2003
    ..We hypothesized that ischemia-reperfusion injury in spinal cord causes DNA damage manifested by 8-oxoG production and activates the DNA repair system involving hMYH, hOGG1, and hMSH2...
  81. ncbi Spontaneous mutation, oxidative DNA damage, and the roles of base and nucleotide excision repair in the yeast Saccharomyces cerevisiae
    A D Scott
    School of Biological Sciences, University of Wales Swansea, UK
    Yeast 15:205-18. 1999
    ..Finally, the repair of Fpg-sensitive sites was examined at the MATalpha and HMLalpha mating type loci, and NER was found to play a role in their removal...
  82. pmc Rat 7,8-dihydro-8-oxoguanine DNA glycosylase: substrate specificity, kinetics and cleavagemechanism at an apurinic site
    M J Prieto Alamo
    Unité 347 INSERM, 80 rue du General Leclerc, 94276 Le Kremlin Bicetre Cedex, France
    Nucleic Acids Res 26:5199-202. 1998
    ..However, rOGG1 acts on a substrate containing an apurinic site by a beta-delta elimination reaction and proceeds through a Schiff base intermediate. Expression of rOGG1 in E.coli fpg mutY suppresses its spontaneous mutator phenotype...
  83. ncbi Multiple colorectal adenomas--is their number up?
    Giancarlo Marra
    N Engl J Med 348:845-7. 2003
  84. pmc Identification of high excision capacity for 5-hydroxymethyluracil mispaired with guanine in DNA of Escherichia coli MutM, Nei and Nth DNA glycosylases
    Masaki Hori
    Laboratory of Radiation Biology, Graduate School of Science, Kyoto University, Kitashirakawa Oiwakecho, Sakyo ku, Kyoto 606 8502, Japan
    Nucleic Acids Res 31:1191-6. 2003
    ..In E.coli, the 5hmU-DNA glycosylase activities of MutM, Nei and Nth may play critical roles in the repair of 5hmU:G mispairs to avoid 5mC to T transitions...
  85. ncbi Structure and function in the uracil-DNA glycosylase superfamily
    L H Pearl
    Section of Structural Biology and CRC DNA Repair Enzyme Group, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, SW3 6JB, London, UK
    Mutat Res 460:165-81. 2000
    ....
  86. pmc Thermostable repair enzyme for oxidative DNA damage from extremely thermophilic bacterium, Thermus thermophilus HB8
    T Mikawa
    Department of Biology, Graduate School of Science, Osaka University, 1 1 Machikaneyama cho, Toyonaka, Osaka 560, Japan
    Nucleic Acids Res 26:903-10. 1998
    ..6 and 16.2 kcal/mol-1, respectively. Thermus thermophilus MutM protein showed 8-oxoguanine DNA glycosylase activity in vitro at both low and high temperatures...
  87. ncbi Aerobiosis increases the genomic guanine plus cytosine content (GC%) in prokaryotes
    Hugo Naya
    Laboratorio de Organización y Evolución del Genoma, Facultad de Ciencias, Igua 4225, Montevideo 11400, Uruguay
    J Mol Evol 55:260-4. 2002
    ..This is the first time that a link between a metabolic character and GC% has been found, independently of phylogenetic relationships and with a statistically significant amount of data...
  88. ncbi Mechanism of action of Escherichia coli formamidopyrimidine N-glycosylase: role of K155 in substrate binding and product release
    L Rabow
    Division of Cancer Biology, Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia 30335, USA
    Prog Nucleic Acid Res Mol Biol 68:223-34. 2001
    ..This is consistent with the idea that K155A dissociates prematurely from the covalent complex, leading to a higher turnover number observed for K155A for DNA substrate containing an AP site...
  89. ncbi Multiple DNA glycosylases for repair of 8-oxoguanine and their potential in vivo functions
    T K Hazra
    Sealy Center for Molecular Science, Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Prog Nucleic Acid Res Mol Biol 68:193-205. 2001
    ..The physiological significance of multiple OGGs and their in vivo reaction mechanisms remain to be elucidated by further studies...
  90. ncbi Alteration of DNA base excision repair enzymes hMYH and hOGG1 in hydrogen peroxide resistant transformed human breast cells
    Y Gu
    Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA
    Med Sci Monit 7:861-8. 2001
    ..CONCLUSIONS: Our results demonstrated, for the first time, that alteration of base excision repair pathways is correlated to cell resistance to oxidative stress...
  91. ncbi Ethanol modulates rat hepatic DNA repair functions
    P Navasumrit
    Cancer Research Campaign Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK
    Alcohol Alcohol 36:369-76. 2001
    ..These studies indicate possible mechanisms for the co-carcinogenic effects of ethanol...
  92. pmc Repair of oxidative DNA damage in Drosophila melanogaster: identification and characterization of dOgg1, a second DNA glycosylase activity for 8-hydroxyguanine and formamidopyrimidines
    C Dherin
    CEA, Departement de Radiobiologie et Radiopathologie, UMR217 CNRS CEA, Radiobiologie Moléculaire et Cellulaire, 60 rue du Général Leclerc, BP6, 92265 Fontenay aux Roses, France
    Nucleic Acids Res 28:4583-92. 2000
    ..Therefore, Drosophila possesses two DNA glycosylase activities that can excise 8-OH-Gua and formamidopyrimidines from DNA, dOgg1 and the ribosomal protein S3...
  93. pmc DNA repair and sequence context affect (1)O(2)-induced mutagenesis in bacteria
    L F Agnez-Lima
    , Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil
    Nucleic Acids Res 29:2899-903. 2001
    ..Thus, the kind of repair and the mutagenesis associated with (1)O(2)-induced DNA damage are linked to the context of the damaged sequence...
  94. pmc hMYH cell cycle-dependent expression, subcellular localization and association with replication foci: evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs
    I Boldogh
    Department of Microbiology, Sealy Center for Environmental Health and Medicine, University of Texas Medical Branch, Galveston, TX 77555-1071 USA
    Nucleic Acids Res 29:2802-9. 2001
    ..The cell cycle-dependent expression and localization of hMYH at sites of DNA replication suggest a role for this glycosylase in immediate post-replication DNA base excision repair...
  95. pmc Base excision of oxidative purine and pyrimidine DNA damage in Saccharomyces cerevisiae by a DNA glycosylase with sequence similarity to endonuclease III from Escherichia coli
    L Eide
    Department of Molecular Biology, University of Oslo, National Hospital, Norway
    Proc Natl Acad Sci U S A 93:10735-40. 1996
    ..S. cerevisiae NTG1 does not have the [4Fe-4S] cluster DNA binding domain characteristic of the other members of this family...
  96. pmc A novel fluorometric oligonucleotide assay to measure O( 6)-methylguanine DNA methyltransferase, methylpurine DNA glycosylase, 8-oxoguanine DNA glycosylase and abasic endonuclease activities: DNA repair status in human breast carcinoma cells overexpressin
    E L Kreklau
    Department of Pharmacology, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Nucleic Acids Res 29:2558-66. 2001
    ....
  97. pmc Repair of hydantoins, one electron oxidation product of 8-oxoguanine, by DNA glycosylases of Escherichia coli
    T K Hazra
    Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 6.136 Medical Research Building, Route 1079, Galveston, TX 77555, USA
    Nucleic Acids Res 29:1967-74. 2001
    ..C pairs. In contrast, MutY does not significantly inhibit Nei for any Gh(Sp) base pair. These results suggest a protective function for MutY in preventing mutation as a result of A (G) incorporation opposite Gh(Sp) during DNA replication...
  98. pmc Recombinational repair is critical for survival of Escherichia coli exposed to nitric oxide
    E J Spek
    Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Bacteriol 183:131-8. 2001
    ..can induce. Furthermore, the importance of recombinational repair for cellular survival of NO(.) exposure reveals a potential susceptibility factor for invading microbes...
  99. ncbi Somatic mutations and single nucleotide polymorphisms of base excision repair genes involved in the repair of 8-hydroxyguanine in damaged DNA
    K Shinmura
    Biology Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, 104-0045, Tokyo, Japan
    Cancer Lett 166:65-9. 2001
    ..Differences in the oh(8)G repair activities of MYH, APEX and OGG1 proteins due to somatic mutations and SNPs can be involved in human carcinogenesis...
  100. ncbi The Drosophila S3 multifunctional DNA repair/ribosomal protein protects Fanconi anemia cells against oxidative DNA damaging agents
    M R Kelley
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, 702 Barnhill Dr, Room 2600, Indianapolis, IN 46202, USA
    Mutat Res 485:107-19. 2001
    ..Based on these findings, we would predict other oxidative repair proteins, or oxidative scavengers, could serve as protective agents against the oxidative DNA damage that occurs in FA...
  101. ncbi Properties and biological functions of the NTH and FPG proteins of Escherichia coli: two DNA glycosylases that repair oxidative damage in DNA
    S Boiteux
    LA 147 CNRS, U140 INSERM, Institut Gustave Roussy, Villejuif, France
    J Photochem Photobiol B 19:87-96. 1993
    ....

Research Grants57

  1. TRANSITION STATE ANALYSIS OF ENZYMATIC REACTIONS
    Vern Schramm; Fiscal Year: 2007
    ..unreadable]..
  2. PERTUSSIS, DIPHTHERIA, CHOLERA TOXINS-INHIBITOR DESIGN
    Vern Schramm; Fiscal Year: 2003
    ..The goal of this work is to extend transition state inhibitor design to the complex reactions catalyzed by bacterial ADP-ribosylating toxins. ..
  3. 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. ..
  4. 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. ..
  5. MOR expressing neurons in pain and morphine analgesia
    RONALD WILEY; Fiscal Year: 2004
    ..Many valuable future experiments and clinical applications may be possible if dermorphin-saporin proves effective. ..
  6. Phase II SBIR: WHI-07: A Novel Dual-Function Microbicide
    OSMOND D CRUZ; Fiscal Year: 2005
    ....
  7. PHI 346: A Novel Dual-Function Microbicide
    OSMOND D CRUZ; Fiscal Year: 2003
    ..Following successful completion of the Phase I in vivo efficacy studies, gel formulation of PHI-346 will be further explored as a vaginal dual-function microbicide in Phase II. ..
  8. Stampidine: A Novel Broad-Spectrum Anti-HIV Microbicide
    OSMOND D CRUZ; Fiscal Year: 2005
    ..Specific Aims 1 and 2 may provide the foundation for the clinical development of STAMP in Phase II studies as a safe, effective broad-spectrum anti-HIV microbicide without conception-inhibiting functions. ..
  9. High Throughput Assay:Topoisomerase Enzyme Targets (RMI)
    JAMES STIVERS; Fiscal Year: 2005
    ..The utility of the assay has been validated, by screening a 2000 member small molecule library from which several novel lead compounds have been identified that specifically target a poxvirus family topoisomerase. ..
  10. Vanadocenes as a New Class of Spermicidal Drugs
    OSMOND D CRUZ; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  11. Developmental Affects of Ritalin on Brain
    TERESA MILNER; Fiscal Year: 2004
    ..Determining how therapeutic dosage regimens effect these transmitter systems is critical in understanding the safety of long-term therapeutic doses of MPH administered to children and adolescents with ADHD and other related disorders. ..
  12. 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. ..
  13. PHI-443: Novel Non-Spermicidal Anti-HIV Microbicide
    OSMOND D CRUZ; Fiscal Year: 2003
    ..Specific Aims 1 and 2 may provide the foundation for the clinical development of PHI-443 in Phase II studies as a safe, effective broad-spectrum anti-HIV microbicide without conception-inhibiting functions. ..
  14. METVAN: A Novel Anticancer Agent
    OSMOND D CRUZ; Fiscal Year: 2003
    ..The knowledge gained from these studies described under Specific Aims 1-2 is expected to facilitate the design of innovative treatment regimens employing METVAN for metastatic breast cancer and brain tumor patients. ..
  15. NOVEL CONTRACEPTIVES WITH ANTI-HIV ACTIVITY
    OSMOND D CRUZ; Fiscal Year: 2001
    ..The preclinical data on in vivo efficacies of WHI-05 and WHI-07 will be essential to further explore the utility of these novel drugs for clinical studies in human patients. ..
  16. FLP-102: Rationally Engineered Antiviral Protein
    OSMOND D CRUZ; Fiscal Year: 2003
    ..The preclinical data on FLP-102 will be essential to further explore the utility of this novel recombinant PAP mutant for Phase II. ..
  17. Regulatory Functions of APE1 - An Essential Repair Protein
    Sankar Mitra; Fiscal Year: 2010
    ..Furthermore, our studies should help identify APE1-regulated key signaling pathways in tumor induction and promotion which could be potential targets for cancer therapy. ..
  18. Plasmodium vivax:Proteomic Analysis of Asexual and Sporozoite Stages
    Liwang Cui; Fiscal Year: 2007
    ..Its recent resurgence in prevalence and emergence of drug- resistant parasite strains have raised a great concern for the future control of malaria. [unreadable] [unreadable] [unreadable]..
  19. Therapeutic/Mechanistic Role of Ape1 in Germ Cell Tumors
    Mark Kelley; Fiscal Year: 2007
    ..If any mutants are shown to sensitize the GCT cell lines to chemo-/IR agents, as expected, this will set the stage for future gene therapy approaches to sensitize GCT's to therapy. ..
  20. Fetal arsenic-nutrient interaction in adult-onset cancer
    Kenneth Beckman; Fiscal Year: 2007
    ..The proposed research will investigate the potential links between exposure to environmental toxicants and dietary nutrition in utero that may contribute significantly to human cancer. [unreadable] [unreadable] [unreadable]..
  21. Isolation of Pancreatic Islets by FACS
    DOUGLAS LAPPI; Fiscal Year: 2002
    ..The method proposed here is patentable and will be of substantial commercial value for licensing for the technology and distributing the islets. ..
  22. BIFUNCTIONAL OPIOID/CCK LIGANDS FOR PAIN
    Frank Porreca; Fiscal Year: 2006
    ..This novel mechanism of action should yield therapeutic utility as well as provide an increased understanding of opioid-CCK interactions in normal and pathological pain states. ..
  23. Identification of the ribosomal target of Shiga-like toxins
    NILGUN TUMER; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  24. NEUTROPHINS AND RETINAL DEVELOPMENT
    Janet Sparrow; Fiscal Year: 2001
    ..The use of neurotrophins in conjunction with gene therapy or transplantation may also have potential for reversing retinal degenerative changes and lead to the restoration of vision. ..
  25. Development of a Diagnostic Test for Alzheimer's Disease
    Mark Lovell; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  26. CSF AND THE CENTRAL CHEMICAL CONTROL OF BREATHING
    Eugene Nattie; Fiscal Year: 2008
    ..abstract_text> ..
  27. Imbalancing DNA BER to enhance Ovarian Tumor Sensitivity
    Mark Kelley; Fiscal Year: 2008
    ..abstract_text> ..
  28. Thymineless stress, DNA repair and recombination
    Michael Wyatt; Fiscal Year: 2008
    ..Because BER and recombination normally contribute to genome stability, these questions have an added significance when current cancer therapies can themselves induce DNA damage. ..
  29. Inhibition of Neurotransmission in Specific Neuronal Populations
    DOUGLAS LAPPI; Fiscal Year: 2008
    ..Therapeutic applications for the treatment of neuropsychiatric and other maladies could result from this technology, but are not the focus of this application. ..
  30. Repair of oxidative damage in mammalian genomes
    Tapas K Hazra; Fiscal Year: 2010
    ..abstract_text> ..
  31. Hindbrain Mechanisms of Hypoglycemia Unawareness
    W Ritter; Fiscal Year: 2007
    ..abstract_text> ..
  32. Development of a cell-based method for high-throughput drug screening in malaria
    Liwang Cui; Fiscal Year: 2008
    ..To facilitate antimalarial drug discovery, we propose to develop a highly sensitive, cell-based, one-step luminescent drug screen assay for high throughput screening of large chemical libraries. [unreadable] [unreadable] [unreadable]..
  33. HYPOXIA-INDUCED DNA DAMAGE AND REPAIR IN THE RAT BRAIN
    Ella W Englander; Fiscal Year: 2010
    ..abstract_text> ..
  34. NEUROBIOLOGICAL MECHANISMS OF ALCOHOL DRINKING
    James Smith; Fiscal Year: 2002
    ..The proposed experiments will hopefully add significant new information to our understanding of the processes underlying alcohol abuse. ..
  35. Translational Control in Plasmodium Sexual Development
    Liwang Cui; Fiscal Year: 2005
    ....
  36. DHEAS, SULFATASE INHIBITION & COGNITION IN LESIONED RATS
    David Johnson; Fiscal Year: 2003
    ..Hippocampal levels of the neurotransmitters, ACh, glutamate and GABA as well as acetylcholinesterase activity in the basal forebrain will be determined. ..
  37. DNA Damage Clusters: Repair in Mammalian Cells
    Betsy Sutherland; Fiscal Year: 2004
    ..Further, knowledge of conditions affecting formation of clustered damages, and cellular paths for dealing with them could allow the design of more effective radiation therapies. ..
  38. Impulsivity and Neural Processing of Rewards
    MARK TODTENKOPF; Fiscal Year: 2005
    ..abstract_text> ..
  39. OXIDATIVE DNA DAMAGE AND REPAIR IN CNS CELLS
    Mark Kelley; Fiscal Year: 2003
    ..abstract_text> ..
  40. Effect of dietary components on DNA repair
    Michael Wyatt; Fiscal Year: 2004
    ..This information will be very useful for planning future epidemiological studies and in the designing of strategies for the prevention of human lung cancer. ..
  41. A Specific Tool for Targeting Neurodegeneration
    DOUGLAS LAPPI; Fiscal Year: 2003
    ..Another important asset of a mouse-specific research tool is the ability of the researcher to combine their use with transgenic models. ..
  42. Estrogenic-cholinergic interactions in memory modulation
    KARYN FRICK; Fiscal Year: 2004
    ..abstract_text> ..
  43. Monoclonal Antibodies to Target Neuronal Populations
    DOUGLAS LAPPI; Fiscal Year: 2005
    ..Despite widespread use of recombinant antibodies in cancer biology with their ability to be modified through the construction of fusion proteins, they are still extremely rare and make this a novel approach. ..
  44. Cholinergic modulation of IEG expression
    ANN POWER; Fiscal Year: 2006
    ..Experiment III will investigate which signaling cascades (e.g., protein kinases) are involved in effects of mR activation on memory and immediate early gene expression. ..
  45. Enzyme Repair of Excoyclic Adducts
    Bo Hang; Fiscal Year: 2005
    ..abstract_text> ..
  46. Tetrahymena Genome Sequencing Project
    Jonathan Eisen; Fiscal Year: 2005
    ....
  47. Drug Development of a Chronic Pain Therapeutic
    DOUGLAS LAPPI; Fiscal Year: 2005
    ..Finally, GMP-grade SP-SAP will be synthesized in preparation for clinical trial. ..
  48. Mechanism of action of ricin A chain
    NILGUN TUMER; Fiscal Year: 2005
    ..These studies will aid in the design of protection strategies against toxins that are classified as high-risk candidates for bioterrorism. ..
  49. Hindbrain mechanisms of hypoglycemia unawarness
    Sue Ritter; Fiscal Year: 2005
    ..Corticosterone infusions and specific stressors with differing effects on corticosterone secretion will be examined for their ability to induce HAAF. ..
  50. NOVEL TUMOR SUPPRESSOR GENES IN A TRANSGENIC MOUSE MODEL
    Eric Radany; Fiscal Year: 2002
    ..2. Continue high resolution mapping of Loh5 based on allelic loss in tumors. New, single nucleotide polymorphism markers will be derived for the region of mouse chromosome 4 that contains this locus. ..
  51. Hormone and enrichment effects on memory in aging mice
    KARYN FRICK; Fiscal Year: 2009
    ..Elucidation of these issues may ultimately lead to the development of safer and more effective treatments to prevent cognitive decline and dementia in women ..
  52. 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. ..
  53. Neurotransmission evoked by 5HT-dependent luminal factor
    Ying Li; Fiscal Year: 2005
    ..Finally, we will examine the roles of various neurotransmitters in the DMN in the mediation of pancreatic secretion stimulated by luminal 5HT-dependent factors using a conscious rat model. ..
  54. NEUROBIOLOGICAL MECHANISMS OF DRUG REINFORCEMENT
    James Smith; Fiscal Year: 2008
    ..abstract_text> ..
  55. EFFECTS OF EXCITOTOXIC INJURY ON SPINAL SENSORY PATHWAYS
    Robert Yezierski; Fiscal Year: 2003
    ..abstract_text> ..
  56. DbpA/B proteins of Borrelia burgdorferi & Lyme arthritis
    Nikhat Parveen; Fiscal Year: 2005
    ..This study will characterize the role of two spirochete lipoprotein adhesins in Lyme arthritis in the murine model. ..