site directed mutagenesis


Summary: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

Top Publications

  1. pmc An efficient one-step site-directed and site-saturation mutagenesis protocol
    Lei Zheng
    Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, CH 3012 Berne, Switzerland
    Nucleic Acids Res 32:e115. 2004
  2. ncbi Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels
    Martin Tristani-Firouzi
    Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
    J Biol Chem 277:18994-9000. 2002
  3. ncbi Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Genet 30:377-84. 2002
  4. ncbi Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein
    Nathan C Shaner
    Nat Biotechnol 22:1567-72. 2004
  5. ncbi Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6
    J A Ballesteros
    Novasite Pharmaceuticals, Inc, San Diego, California 92121, USA
    J Biol Chem 276:29171-7. 2001
  6. pmc Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation
    Baron Chanda
    Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    J Gen Physiol 120:629-45. 2002
  7. ncbi DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected]
    C D Mol
    Skaggs Institute for Chemical Biology, and the Department of Molecular Biology, La Jolla, California 92037 1027, USA
    Nature 403:451-6. 2000
  8. pmc Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide
    S Chen
    Department of Pharmacology, ColumbiaUniversity, New York, New York 10032, USA
    J Gen Physiol 117:491-504. 2001
  9. pmc Site-directed, Ligase-Independent Mutagenesis (SLIM): a single-tube methodology approaching 100% efficiency in 4 h
    Joyce Chiu
    School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    Nucleic Acids Res 32:e174. 2004
  10. ncbi Molecular determinants of state-dependent block of Na+ channels by local anesthetics
    D S Ragsdale
    Department of Pharmacology, University of Washington, Seattle 98195
    Science 265:1724-8. 1994

Detail Information

Publications355 found, 100 shown here

  1. pmc An efficient one-step site-directed and site-saturation mutagenesis protocol
    Lei Zheng
    Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, CH 3012 Berne, Switzerland
    Nucleic Acids Res 32:e115. 2004
    ..This method should be useful to facilitate the preparation of high-quality site saturation libraries...
  2. ncbi Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels
    Martin Tristani-Firouzi
    Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
    J Biol Chem 277:18994-9000. 2002
    ..Moreover, our findings suggest that the C-terminal ends of S4 and S6 are in close proximity at hyperpolarized membrane potentials...
  3. ncbi Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Genet 30:377-84. 2002
    ..The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype...
  4. ncbi Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein
    Nathan C Shaner
    Nat Biotechnol 22:1567-72. 2004
    ..Three monomers with distinguishable hues from yellow-orange to red-orange have higher quantum efficiencies...
  5. ncbi Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6
    J A Ballesteros
    Novasite Pharmaceuticals, Inc, San Diego, California 92121, USA
    J Biol Chem 276:29171-7. 2001
    ..49), Arg(3.50), and Glu(6.30) may constitute a common switch governing the activation of many rhodopsin-like G-protein-coupled receptors...
  6. pmc Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation
    Baron Chanda
    Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    J Gen Physiol 120:629-45. 2002
    ..These experiments allow us to map structural features onto the kinetic landscape of a sodium channel during activation...
  7. ncbi DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected]
    C D Mol
    Skaggs Institute for Chemical Biology, and the Department of Molecular Biology, La Jolla, California 92037 1027, USA
    Nature 403:451-6. 2000
  8. pmc Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide
    S Chen
    Department of Pharmacology, ColumbiaUniversity, New York, New York 10032, USA
    J Gen Physiol 117:491-504. 2001
    ..Finally, differences in Ih channel properties recorded in cell-free patches versus intact oocytes are shown to be due, in part, to modulation of Ih by basal levels of cAMP in intact cells...
  9. pmc Site-directed, Ligase-Independent Mutagenesis (SLIM): a single-tube methodology approaching 100% efficiency in 4 h
    Joyce Chiu
    School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    Nucleic Acids Res 32:e174. 2004
    ..In this study, SLIM was employed to create sequence insertions, deletion and substitution within bacteriophage T7 gene 5. The overall efficiency for obtaining the desired product was >95%...
  10. ncbi Molecular determinants of state-dependent block of Na+ channels by local anesthetics
    D S Ragsdale
    Department of Pharmacology, University of Washington, Seattle 98195
    Science 265:1724-8. 1994
    ..The results define the location of the local anesthetic receptor site in the pore of the Na+ channel and identify molecular determinants of the state-dependent binding of local anesthetics...
  11. pmc The role of the putative inactivation lid in sodium channel gating current immobilization
    M F Sheets
    Nora Eccles Harrison Cardiovascular Research and Training Institute and The Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84112, USA
    J Gen Physiol 115:609-20. 2000
    ..Taken together with previous reports, these data also suggest that S4 in domain III contributes to charge immobilization only after binding of the inactivation lid...
  12. ncbi Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting
    P V Schu
    Division of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine
    Science 260:88-91. 1993
    ..VPS34 encodes a yeast PI 3-kinase, and this enzyme appears to regulate intracellular protein trafficking decisions...
  13. pmc An efficient one-step site-directed deletion, insertion, single and multiple-site plasmid mutagenesis protocol
    Huanting Liu
    SSPF, Centre for Biomolecular Science, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK
    BMC Biotechnol 8:91. 2008
    ..Although many site-directed mutagenesis methods have been developed, a simple, quick and multi-applicable method is still desirable...
  14. pmc The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4
    M F Sheets
    The Nora Eccles Harrison Cardiovascular Research and Training Institute and Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84112, USA
    Biophys J 77:747-57. 1999
  15. ncbi Biophysical and molecular mechanisms of Shaker potassium channel inactivation
    T Hoshi
    Department of Molecular and Cellular Physiology, Stanford University, School of Medicine, CA 94305
    Science 250:533-8. 1990
    ..A region near the amino terminus with an important role in inactivation has now been identified. The results suggest a model where this region forms a cytoplasmic domain that interacts with the open channel to cause inactivation...
  16. ncbi Dual phosphorylation controls Cdc25 phosphatases and mitotic entry
    Dmitry V Bulavin
    Gene Response Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 5:545-51. 2003
    ..We propose that this pathway ensures that Cdc2 remains active once mitosis is initiated and is a key control mechanism for maintaining the proper order of cell-cycle transitions...
  17. pmc Mutations in the K+ channel signature sequence
    L Heginbotham
    Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
    Biophys J 66:1061-7. 1994
    ..Furthermore, the results illustrate that the hydroxyl groups at the third and fourth positions, and the aromatic group at position seven, are not essential in determining K+ selectivity...
  18. ncbi How does an enzyme evolved in vitro compare to naturally occurring homologs possessing the targeted function? Tyrosine aminotransferase from aspartate aminotransferase
    Steven C Rothman
    Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall 3206, Berkeley, CA 94720 3206, USA
    J Mol Biol 327:593-608. 2003
  19. ncbi Is the glutamate residue Glu-373 the proton acceptor of the excitatory amino acid carrier 1?
    Christof Grewer
    Max Planck Institut fur Biophysik, Kennedyallee 70, Frankfurt D 60596, Germany
    J Biol Chem 278:2585-92. 2003
    ..The function of alanine-serine-cysteine transporter is neither potassium- nor proton-dependent. Consequently, our results emphasize the general importance of glutamate and aspartate residues for proton transport across membranes...
  20. pmc Regulation of hepatitis C virion production via phosphorylation of the NS5A protein
    Timothy L Tellinghuisen
    The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA
    PLoS Pathog 4:e1000032. 2008
    ..The ability to uncouple virus production from RNA replication, as described herein, may be useful in understanding HCV assembly and may be therapeutically important...
  21. pmc Discovery of natural nicking endonucleases Nb.BsrDI and Nb.BtsI and engineering of top-strand nicking variants from BsrDI and BtsI
    Shuang yong Xu
    New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA
    Nucleic Acids Res 35:4608-18. 2007
    ..Top-strand specific nicking variants, Nt.BsrDI and Nt.BtsI, were successfully engineered by combining the catalytic-deficient B subunit with wild-type A subunit...
  22. ncbi Gemin5-snRNA interaction reveals an RNA binding function for WD repeat domains
    Chi Kong Lau
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, USA
    Nat Struct Mol Biol 16:486-91. 2009
    ..The WD repeat domain is thus a previously undescribed RNA binding domain, and we suggest that the presence of WD repeats should be considered as predictive of potential function in RNA binding...
  23. pmc Structure of the two transmembrane Cu+ transport sites of the Cu+ -ATPases
    Manuel González-Guerrero
    Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, USA
    J Biol Chem 283:29753-9. 2008
    ..3 fM(-1), Site II K(a)=1.1 fM(-1)), in conjunction with reversible direct Cu(+) transfer from chaperones, points to a transport mechanism where backward release of free Cu(+) to the cytoplasm is largely prevented...
  24. ncbi Caspase-mediated proteolysis of the polyglutamine disease protein ataxin-3
    Sarah J Shoesmith Berke
    Neuroscience Graduate Program and Department of Neurology, University of Iowa, Iowa City, Iowa 52242, USA
    J Neurochem 89:908-18. 2004
    ..Finally, caspase-mediated cleavage of expanded ataxin-3 resulted in increased ataxin-3 aggregation, suggesting a potential role for caspase-mediated proteolysis in spinocerebellar ataxia type-3 pathogenesis...
  25. ncbi Mapping structural determinants of biological activities in snake venom phospholipases A2 by sequence analysis and site directed mutagenesis
    Lucimara Chioato
    Department of Biochemistry and Immunology, FMRP USP, Universidade de Sao Paulo, Brazil
    Toxicon 42:869-83. 2003
    ..predict the structural determinants of these effects, and the predictions are subsequently evaluated by site directed mutagenesis experiments and functional assays...
  26. pmc Voltage-controlled gating at the intracellular entrance to a hyperpolarization-activated cation channel
    Brad S Rothberg
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    J Gen Physiol 119:83-91. 2002
    ..Together, these results are consistent with a voltage-controlled structure at the intracellular side of the spHCN channel that can gate the flow of cations through the pore...
  27. ncbi Molecular basis of gating charge immobilization in Shaker potassium channels
    F Bezanilla
    Department of Physiology, UCLA School of Medicine 90024
    Science 254:679-83. 1991
    ..The gating transitions between closed states of the channel appear not to be independent, suggesting that the channel subunits interact during activation...
  28. ncbi The nuclear dot protein sp100, characterization of domains necessary for dimerization, subcellular localization, and modification by small ubiquitin-like modifiers
    T Sternsdorf
    Heinrich Pette Institut fur experimentelle Virologie und Immunologie an der Universitat Hamburg, Martinistrasse 52, D 20251 Hamburg, Germany
    J Biol Chem 274:12555-66. 1999
    ..Taken together, our studies indicate the existence of well defined Sp100 domains with functions in ND targeting, nuclear import, nuclear SUMOylation, and protein-protein interaction...
  29. ncbi Glycophorin A dimerization is driven by specific interactions between transmembrane alpha-helices
    M A Lemmon
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511
    J Biol Chem 267:7683-9. 1992
    ..This approach allows the interface between interacting helices to be defined...
  30. pmc Highly conserved NIKS tetrapeptide is functionally essential in eukaryotic translation termination factor eRF1
    Ludmila Frolova
    Engelhardt Institute of Molecular Biology, Moscow, Russia
    RNA 8:129-36. 2002
    ..Reduction in ribosome binding revealed for Ile62, Ser64, Arg65, and Arg68 mutants argues in favor of the essential role played by the right part of the NIKS loop in interaction with the ribosome, most probably with ribosomal RNA...
  31. pmc The structure and function of the beta 2-adaptin appendage domain
    D J Owen
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
    EMBO J 19:4216-27. 2000
    ..This results in the displacement of the other ligands from the beta 2 appendage. Thus clathrin binding to an AP2-accessory protein complex would cause the controlled release of accessory proteins at sites of vesicle formation...
  32. ncbi Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease
    Naohiro Inohara
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 278:5509-12. 2003
    ..Because muramyl dipeptide is the essential structure of peptidoglycan required for adjuvant activity, these results also have implications for understanding adjuvant function and effective vaccine development...
  33. pmc Role of the C-terminal domain in inactivation of brain and cardiac sodium channels
    M Mantegazza
    Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 98:15348-53. 2001
    ..Thus, the C terminus has a strong influence on kinetics and voltage dependence of inactivation in brain Na(v)1.2 and cardiac Na(v)1.5 channels and is primarily responsible for their differing rates of channel inactivation...
  34. ncbi Acetylcholinesterase. Two types of modifications confer resistance to insecticide
    D Fournier
    Centre de recherche d Antibes, Laboratoire de Biologie des Invertébrés, France
    J Biol Chem 267:14270-4. 1992
    ..Flies mutant for acetylcholinesterase and rescued with a minigene mutagenized for this same transition produced an altered enzyme which renders flies resistant to pesticides...
  35. ncbi Phosphorylation of annexin I by TRPM7 channel-kinase
    Maxim V Dorovkov
    Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Biol Chem 279:50643-6. 2004
    ..The N-terminal region plays a crucial role in interaction of annexin 1 with other proteins and membranes, and therefore, phosphorylation of annexin 1 at Ser5 by TRPM7 kinase may modulate function of annexin 1...
  36. ncbi Homophilic adhesion of human CEACAM1 involves N-terminal domain interactions: structural analysis of the binding site
    S M Watt
    Stem Cell Laboratory, National Blood Service, Nuffield Department of Clinical and Laboratory Sciences, and the MRC Molecular Haematology Unit, Institute of Molecular Medicine, Oxford, United Kingdom
    Blood 98:1469-79. 2001
  37. pmc Tryptophan scanning of D1S6 and D4S6 C-termini in voltage-gated sodium channels
    Sho Ya Wang
    Department of Biology, State University of New York at Albany, Albany, New York, USA
    Biophys J 85:911-20. 2003
    ..Implications of these results will be discussed in terms of indirect allosteric modulations via amino acid substitutions and/or a direct involvement of S6 C-termini in Na(+) channel gating...
  38. pmc Structure of Thermotoga maritima stationary phase survival protein SurE: a novel acid phosphatase
    R G Zhang
    Biosciences Division and Structural Biology Center, Argonne National Laboratory, 9700 South Cass Avenue, Building 202, Argonne, IL 60439, USA
    Structure 9:1095-106. 2001
    ..coli subjected to high-temperature growth. The pcm and surE genes are highly conserved in bacteria, archaea, and plants...
  39. pmc Structural basis for autoantibody recognition of phosphatidylserine-beta 2 glycoprotein I and apoptotic cells
    B A Cocca
    Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, PA 19129, USA
    Proc Natl Acad Sci U S A 98:13826-31. 2001
    ..The results suggest that, in autoimmunity, B cells with Ig receptors for apoptotic cells and DNA are positively selected, and that the antibodies they produce have the potential to affect the clearance and processing of apoptotic cells...
  40. pmc Effect of S6 tail mutations on charge movement in Shaker potassium channels
    Shinghua Ding
    Department of Physiology, Institute of Hyperexcitability, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA
    Biophys J 84:295-305. 2003
    ..Taken together, our results suggest that the tail end of S6 plays an important role in coupling between activation gating and charge movement...
  41. ncbi Alpha4 integrin binding interfaces on VCAM-1 and MAdCAM-1. Integrin binding footprints identify accessory binding sites that play a role in integrin specificity
    P Newham
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom
    J Biol Chem 272:19429-40. 1997
    ..The analogous region in MAdCAM-1 is markedly different in size and sequence and when mutated abolishes integrin binding activity...
  42. pmc Functional significance of the specific sites phosphorylated in desmin at cleavage furrow: Aurora-B may phosphorylate and regulate type III intermediate filaments during cytokinesis coordinatedly with Rho-kinase
    Aie Kawajiri
    Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa ku, Nagoya 464 8681, Japan
    Mol Biol Cell 14:1489-500. 2003
    ..The results presented here suggest the possibility that Aurora-B may regulate cleavage furrow-specific phosphorylation and segregation of type III IFs coordinatedly with Rho-kinase during cytokinesis...
  43. ncbi Oxidized galectin-1 promotes axonal regeneration in peripheral nerves but does not possess lectin properties
    Y Inagaki
    Pharmaceutical Research Laboratory, Kirin Brewery Co Ltd, Takasaki, Japan
    Eur J Biochem 267:2955-64. 2000
    ..These results indicate that galectin-1 promotes axonal regeneration only in the oxidized form containing three intramolecular disulfide bonds, not in the reduced form which exhibits lectin activity...
  44. pmc NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein
    Sabine Brandt
    Department of Medical Microbiology, Otto von Guericke University, Leipziger Strasse 44, D 39120 Magdeburg, Germany
    Proc Natl Acad Sci U S A 102:9300-5. 2005
    ..Thus, CagA is a multifunctional protein capable of effecting both actin remodeling and potentiation of chemokine release...
  45. pmc Crystal structure of the beta beta alpha-Me type II restriction endonuclease Hpy99I with target DNA
    Monika Sokolowska
    International Institute of Molecular and Cell Biology, Trojdena 4, 02 109 Warsaw, Poland
    Nucleic Acids Res 37:3799-810. 2009
    ..g. I-PpoI) and Holliday junction resolvases (e.g. T4 endonuclease VII)...
  46. pmc Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases
    M B Calalb
    Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    Mol Cell Biol 15:954-63. 1995
    ..Our results indicate that phosphorylation of FAK by Src (or other Src family kinases) is an important step in the formation of an active signaling complex...
  47. pmc Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases
    Alexander U Singer
    Ontario Centre for Structural Proteomics, Banting and Best Department for Medical Research, University of Toronto, C H Best Institute, Toronto, Ontario M5G1L5, Canada
    Nat Struct Mol Biol 15:1293-301. 2008
    ..The conserved and essential cysteine residue lies on a flexible, surface-exposed loop surrounded by conserved acidic residues, two of which are crucial for IpaH activity...
  48. ncbi Identification of a new subfamily of HNH nucleases and experimental characterization of a representative member, HphI restriction endonuclease
    Iwona A Cymerman
    Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Trojdena 4, 02 109 Warsaw, Poland
    Proteins 65:867-76. 2006
  49. ncbi Domain III of NS5A contributes to both RNA replication and assembly of hepatitis C virus particles
    Mair Hughes
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    J Gen Virol 90:1329-34. 2009
    ..We propose that although domain III is dispensable for RNA replication, it nevertheless influences this process...
  50. pmc Phage integrases for the construction and manipulation of transgenic mammals
    Roger P Hollis
    Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 5120, USA
    Reprod Biol Endocrinol 1:79. 2003
    ..The results reviewed here introduce these bacteriophage integrases as tools for site-specific modification of the genome for the creation and manipulation of transgenic mammals...
  51. pmc Functional analysis and structural modeling of human APOBEC3G reveal the role of evolutionarily conserved elements in the inhibition of human immunodeficiency virus type 1 infection and Alu transposition
    Yannick Bulliard
    School of Life Sciences and Frontiers in Genetics National Center of Competence in Research, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland
    J Virol 83:12611-21. 2009
  52. ncbi A strategy for the generation of non-aggregating mutants of Anthozoa fluorescent proteins
    Yurii G Yanushevich
    Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia
    FEBS Lett 511:11-4. 2002
    ..The elimination of basic residues located near the N-termini of FPs results in the generation of non-aggregating versions of several FPs, specifically, drFP583 (DsRed), DsRed-Timer, ds/drFP616, zFP506, zFP538, amFP486, and asFP595...
  53. ncbi Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB
    W N Zagotta
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305
    Science 250:568-71. 1990
    ..These results support the proposal that inactivation occurs by a cytoplasmic domain that occludes the ion-conducting pore of the channel...
  54. ncbi Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity
    Edmund N C Newman
    Department of Infectious Diseases, Guy s, King s, and St Thomas School of Medicine, King s College London, London SE1 9RT, United Kingdom
    Curr Biol 15:166-70. 2005
    ..Accordingly, we propose that APOBEC3G can achieve an anti-HIV-1 effect through an undescribed mechanism that is distinct from cytidine deamination...
  55. ncbi A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels
    L Heginbotham
    Department of Neurobiology, Harvard Medical School, Boston, MA 02115
    Science 258:1152-5. 1992
  56. pmc ZipA-induced bundling of FtsZ polymers mediated by an interaction between C-terminal domains
    C A Hale
    Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4960, USA
    J Bacteriol 182:5153-66. 2000
    ..Thus, in addition to the C-terminal FZB domain, the N-terminal domain of ZipA is required for ZipA function. Furthermore, the essential properties of the N domain may be more specific than merely acting as a membrane anchor...
  57. ncbi Amino acid residues involved in gating identified in the first membrane-spanning domain of the rat P2X(2) receptor
    L H Jiang
    Institute of Molecular Physiology, University of Sheffield, Alfred Denny Building, Western Bank, Sheffield S10 2TN, United Kingdom
    J Biol Chem 276:14902-8. 2001
    ..The results suggest that Val(48) at the outer end of the first hydrophobic segment takes part in the gating movement of channel opening...
  58. pmc Blocker state dependence and trapping in hyperpolarization-activated cation channels: evidence for an intracellular activation gate
    K S Shin
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Gen Physiol 117:91-101. 2001
    ..Overall, the observations led us to hypothesize that the residues responsible for ZD7288 block of I(h) channels are located in the pore lining, and are guarded by an intracellular activation gate of the channel...
  59. ncbi Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel
    E Y Isacoff
    Howard Hughes Medical Institute, University of California, San Francisco 94143
    Nature 353:86-90. 1991
    ..The S4-S5 loop, therefore, probably forms part of a receptor for the inactivation gate and lies near the channel's permeation pathway...
  60. ncbi Editors and editing of anti-DNA receptors
    H Li
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Immunity 15:947-57. 2001
    ..Among the edited B cells is a subset of multispecific cells that express multiple receptors. One consequence of multispecificity is partial autoreactivity; these multispecific B cells may contribute to autoimmunity...
  61. pmc Tissue-spanning redox gradient-dependent assembly of native human papillomavirus type 16 virions
    Michael J Conway
    Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
    J Virol 83:10515-26. 2009
    ..These data provide evidence that papillomavirus assembly and maturation is redox-dependent, utilizing multiple steps within both suprabasal and cornified layers...
  62. ncbi Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif
    D W Carr
    Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201 3098
    J Biol Chem 266:14188-92. 1991
    ..These data suggest that anchoring proteins interact with RII alpha via an amphipathic helix binding motif...
  63. pmc The Rho GTPase Rho3 has a direct role in exocytosis that is distinct from its role in actin polarity
    J E Adamo
    Department of Cell Biology, Cell Biology, and Genetics, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Biol Cell 10:4121-33. 1999
    ..These data suggest that Rho3 acts as a key regulator of cell polarity and exocytosis, coordinating several distinct events for delivery of proteins to specific sites on the cell surface...
  64. ncbi Key residues for membrane binding, oligomerization, and pore forming activity of staphylococcal alpha-hemolysin identified by cysteine scanning mutagenesis and targeted chemical modification
    B Walker
    Worcester Foundation for Biomedical Research, Shrewsbury, Massachusetts 01545, USA
    J Biol Chem 270:23065-71. 1995
  65. pmc Coupling between voltage sensors and activation gate in voltage-gated K+ channels
    Zhe Lu
    Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Gen Physiol 120:663-76. 2002
    ..One sequence is the so called S4-S5 linker distal to the voltage-sensing S4, while the other is around the COOH-terminal end of S6, a region containing the actual gate-forming residues...
  66. pmc Individual subunits of the glutamate transporter EAAC1 homotrimer function independently of each other
    Christof Grewer
    University of Miami School of Medicine, 1600 NW 10th Avenue, Miami, Florida 33136, USA
    Biochemistry 44:11913-23. 2005
    ..In conclusion, we propose that EAAC1 assembles as trimers of identical subunits but that the individual subunits in the trimer function independently of each other...
  67. ncbi Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs
    Xiaojun Wang
    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611 3008, USA
    J Mol Biol 320:85-95. 2002
    ..This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity...
  68. pmc A highly efficient recombineering-based method for generating conditional knockout mutations
    Pentao Liu
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
    Genome Res 13:476-84. 2003
    ..This method should also facilitate the generation of knock-in mutations and transgene constructs, as well as expedite the analysis of regulatory elements and functional domains in or near genes...
  69. pmc Distribution of fitness and virulence effects caused by single-nucleotide substitutions in Tobacco Etch virus
    Purificación Carrasco
    Instituto de Biología Molecular y Celular de Plantas CSIC UPV, Avenida de los Naranjos s n, 46022 Valencia, Spain
    J Virol 81:12979-84. 2007
    ..4% increases. Interestingly, the only mutations showing a significant effect on virulence were hypervirulent. Competitive fitness and virulence were uncorrelated traits...
  70. ncbi Importance of phenylalanine 107 in agonist recognition by the 5-hydroxytryptamine(3A) receptor
    L J Steward
    Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, United Kingdom
    Mol Pharmacol 57:1249-55. 2000
    ..These data suggest that F107 is an important determinant of agonist recognition at the 5-HT(3) receptor...
  71. pmc Class-1 translation termination factors: invariant GGQ minidomain is essential for release activity and ribosome binding but not for stop codon recognition
    A Seit-Nebi
    Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, 32 Vavilov Street, 119991 Moscow, Russia
    Nucleic Acids Res 29:3982-7. 2001
    ..The data suggest that the GGQ motif is implicated both in promoting peptidyl-tRNA hydrolysis and binding to the ribosome...
  72. ncbi Site-directed mutagenesis and homology modeling indicate an important role of cysteine 439 in the stability of betaine aldehyde dehydrogenase from Pseudomonas aeruginosa
    Lilian González-Segura
    Laboratorio de Osmorregulación, FES Iztacala, Av de los Barrios 1, Col Los Reyes Iztacala, Tlalnepantla, Edo México 54090, Mexico
    Biochimie 87:1056-64. 2005
    ..To the best of our knowledge, this is the first study of an aldehyde dehydrogenase revealing a residue at the dimer interface involved in holding the dimer, and consequently the tetramer, together...
  73. ncbi Cloning and functional characterization of the smooth muscle ether-a-go-go-related gene K+ channel. Potential role of a conserved amino acid substitution in the S4 region
    Fouzia Shoeb
    Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City 73104, USA
    J Biol Chem 278:2503-14. 2003
    ..These studies define the functional role of a novel isoform of the ether-a-go-go-related gene K(+) channel in smooth muscle...
  74. ncbi Evidence that the Streptomyces developmental protein WhiD, a member of the WhiB family, binds a [4Fe-4S] cluster
    Piotr Jakimowicz
    Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom
    J Biol Chem 280:8309-15. 2005
    ..Each of the four conserved cysteine residues, Cys-23, -53, -56, and -62, was essential for WhiD function in vivo...
  75. ncbi Enzyme catalysis: removing chemically 'essential' residues by site-directed mutagenesis
    A Peracchi
    Dept of Biochemistry and Molecular Biology, University of Parma, 43100, Parma, Italy
    Trends Biochem Sci 26:497-503. 2001
    ..Removal of an 'essential' group often does not abolish activity, but can significantly alter the catalytic mechanism. Such results underscore the sophistication of enzyme catalysis and the functional plasticity of enzyme active sites...
  76. pmc Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation
    R Foster
    Massachusetts General Hospital Cancer Center, Charlestown 02129, USA
    Mol Cell Biol 16:2689-99. 1996
    ..Thus, two unusual structural features of this novel Rho protein suggest a striking evolutionary divergence from the Rho family of GTPases...
  77. pmc Crystal structure determination and site-directed mutagenesis of the Pyrococcus abyssi aCBF5-aNOP10 complex reveal crucial roles of the C-terminal domains of both proteins in H/ACA sRNP activity
    Xavier Manival
    Laboratoire de Maturation des ARN et Enzymologie Moleculaire, UMR 7567 UHP CNRS, Université des Sciences et Techniques Henri Poincaré, Nancy I, 54506 Vandoeuvre les Nancy Cedex, France
    Nucleic Acids Res 34:826-39. 2006
    ..By gel filtration assay, we showed that aNOP10 can dimerize in solution. As both residues Y41 and L48 were needed for dimerization, the dimerization likely takes place by interaction of parallel alpha-helices...
  78. ncbi Structural basis of DNA bridging by barrier-to-autointegration factor
    T C Umland
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Biochemistry 39:9130-8. 2000
    ..A model of BAF bridging DNA via the HhH motif is proposed...
  79. ncbi Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum
    Bernardo J Foth
    Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Parkville, VIC 3010, Australia
    Science 299:705-8. 2003
    ..Similarly, putative Hsp70 (DnaK) binding sites present in the transit peptide proved to be important for correct targeting...
  80. pmc Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods
    Debraj GuhaThakurta
    Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63114, USA
    Genome Res 12:701-12. 2002
    ..The contributions of individual sites toward induction of transcription on HS are nonadditive, which indicates interaction and cross-talk between the sites, possibly through the transcription factors (TFs) binding to these sites...
  81. pmc Characterization of cyclo-acetoacetyl-L-tryptophan dimethylallyltransferase in cyclopiazonic acid biosynthesis: substrate promiscuity and site directed mutagenesis studies
    Xinyu Liu
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Biochemistry 48:11032-44. 2009
    ..Subsequent site-directed mutagenesis studies identified five polar/charged residues and five tyrosine residues within these motifs that are critical for CpaD activity...
  82. pmc Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases
    Yolanda Santiago
    Sangamo BioSciences, Inc, 501 Canal Boulevard, Suite A100, Richmond, CA 94804, USA
    Proc Natl Acad Sci U S A 105:5809-14. 2008
  83. ncbi Expression of the palmitoylation-deficient CD151 weakens the association of alpha 3 beta 1 integrin with the tetraspanin-enriched microdomains and affects integrin-dependent signaling
    Fedor Berditchevski
    Cancer Research UK Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham B15 2TA, United Kingdom
    J Biol Chem 277:36991-7000. 2002
    ..Our results demonstrate that palmitoylation of tetraspanins is critical not only for the organization of the integrin-tetraspanin microdomains but also has a specific role in modulation of adhesion-dependent signaling...
  84. ncbi Direct interaction of a Ca2+-binding loop of synaptotagmin with lipid bilayers
    E R Chapman
    Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, USA
    J Biol Chem 273:13995-4001. 1998
    ..The penetration of C2A into membranes may function to bring components of the fusion machinery into contact with the lipid bilayer to initiate exocytosis...
  85. ncbi A neural-network-based method for predicting protein stability changes upon single point mutations
    Emidio Capriotti
    Laboratory of Biocomputing, CIRB Department of Biology, University of Bologna, Bologna, Italy
    Bioinformatics 20:i63-8. 2004
    ..This allows the application of machine learning techniques to predicting free energy stability changes upon mutation starting from the protein sequence...
  86. ncbi A novel megaprimed and ligase-free, PCR-based, site-directed mutagenesis method
    Wen Chi Tseng
    Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 106, Taiwan
    Anal Biochem 375:376-8. 2008
    ..This method can be further extended to double mutations that are located at distant sites by using two mutagenic oligonucleotides and even to site saturation mutagenesis by introducing randomized codons...
  87. ncbi Molecular dynamics simulations of Alzheimer Abeta40 elongation and lateral association
    Jie Zheng
    Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, Ohio 44325, USA
    Front Biosci 13:3919-30. 2008
  88. ncbi AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha1: involvement in the nuclear import of RNA-binding protein HuR
    Wengong Wang
    Laboratory of Cellular and Molecular Biology, NIA Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 279:48376-88. 2004
    ..Our results point to importin alpha1 as a critical downstream target of AMPK and key mediator of AMPK-triggered HuR nuclear import...
  89. ncbi Localization and characterization of the calsequestrin-binding domain of triadin 1. Evidence for a charged beta-strand in mediating the protein-protein interaction
    Y M Kobayashi
    Departments of Medicine, Biochemistry and Molecular Biology, Physiology and Biophysics, and the Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 275:17639-46. 2000
    ..This small, highly charged beta-strand of triadin may tether calsequestrin to the junctional face membrane, allowing calsequestrin to sequester Ca(2+) in the vicinity of the ryanodine receptor during Ca(2+) uptake and Ca(2+) release...
  90. pmc Functional and biochemical dissection of the structure-specific nuclease ARTEMIS
    Ulrich Pannicke
    Institute for Clinical Transfusion Medicine and Immunogenetics, and Department of Transfusion Medicine, University of Ulm, Ulm, Germany
    EMBO J 23:1987-97. 2004
    ..These results indicate that the hairpin-opening activity of ARTEMIS and/or its overhang endonucleolytic activity are necessary but its exonuclease activity is not sufficient for the process of V(D)J recombination...
  91. pmc Mutational analysis of yeast TFIIB. A functional relationship between Ssu72 and Sub1/Tsp1 defined by allele-specific interactions with TFIIB
    W H Wu
    Department of Biochemistry, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA
    Genetics 153:643-52. 1999
    ..These results demonstrate functional interactions among TFIIB, Ssu72, and Sub1 and suggest that these interactions play a role in the mechanism of start site selection by RNA polymerase II...
  92. pmc Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate
    M Covarrubias
    Department of Anatomy, Pathology, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107
    Neuron 13:1403-12. 1994
    ..The regulatory mechanism reported here may have substantial effects on signal coding in the nervous system...
  93. ncbi Deamidation affects structural and functional properties of human alphaA-crystallin and its oligomerization with alphaB-crystallin
    Ratna Gupta
    Department of Physiological Optics, University of Alabama at Birmingham, Birmingham, Alabama 35294 4390, USA
    J Biol Chem 279:44258-69. 2004
  94. pmc CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells
    Jeroen Witteveldt
    MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK
    J Gen Virol 90:48-58. 2009
  95. pmc Engineering BspQI nicking enzymes and application of N.BspQI in DNA labeling and production of single-strand DNA
    Penghua Zhang
    New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA
    Protein Expr Purif 69:226-34. 2010
    ..Restriction mapping and run-off DNA sequencing of digested products from the partially purified enzyme indicated that it is an EarI isoschizomer with 6-bp recognition, which we named CatHI (CTCTTC N1/N4)...
  96. pmc Structural requirements of bitter taste receptor activation
    Anne Brockhoff
    Department of Molecular Genetics, German Institute of Human Nutrition Potsdam Rehbruecke, 14558 Nuthetal, Germany
    Proc Natl Acad Sci U S A 107:11110-5. 2010
    ..Detailed structure-function analyses of hTAS2Rs may ultimately pave the way for the development of specific antagonists urgently needed for more sophisticated analyses of human bitter taste perception...
  97. ncbi Substitutions of 169Lys and 173Thr in nonstructural protein 1 influence the infectivity and pathogenicity of XJ-160 virus
    Wu Yang Zhu
    State Key Laboratory for Infectious Disease Control and Prevention, Institute for Viral Disease Control and Prevention, China CDC, 100 Yingxin Street, Xuan Wu District, 100052 Beijing, China
    Arch Virol 154:245-53. 2009
    ..These mutations might be associated with the RNA methyltransferase (MTase) activity of nsP1...
  98. ncbi A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling: implications for family B G-protein-coupled receptors
    Alex C Conner
    School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK
    Mol Pharmacol 67:20-31. 2005
    ..P321A-I325P, predicted to restore this conformation, showed wild-type activation. Modeling can also rationalize the effects of transmembrane proline mutants previously reported for another family B GPCR, the VPAC(1) receptor...
  99. ncbi Functional analyses of the domain structure in the Holliday junction binding protein RuvA
    T Nishino
    Department of Structural Biology, Biomolecular Engineering Research Institute BERI, Osaka, Japan
    Structure 6:11-21. 1998
    ..The atomic structure of RuvA should enable critical questions to be addressed about its specific interactions with the Holliday junction and the RuvB protein...
  100. ncbi Intersubunit contacts governing assembly of the mammalian nicotinic acetylcholine receptor
    H J Kreienkamp
    Department of Pharmacology, La Jolla 92093
    Neuron 14:635-44. 1995
    ..The conserved residues I145 and T150 of the gamma subunit promote alpha gamma alpha gamma tetramer formation, whereas the corresponding residues in the delta subunit, K145 and K150, allow only alpha delta dimer formation...
  101. pmc Engineering an enzyme to resist boiling
    B van den Burg
    Department of Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren The Netherlands
    Proc Natl Acad Sci U S A 95:2056-60. 1998
    ..Remarkably, whereas hyperstable enzymes isolated from natural sources often have reduced activity at low temperatures, the 8-fold mutant displayed wild-type-like activity at 37 degrees C...

Research Grants66

  1. Role of Polyamines in MYCN-Amplified Neuroblastoma
    ANDRE BACHMANN; Fiscal Year: 2009
    ..Our research will be useful in the development of novel treatments for the most aggressive forms of the childhood cancer neuroblastoma. ..
    Pi Wan Cheng; Fiscal Year: 2010
    ..Current studies could facilitate the development of therapy for mucus hypersecretory diseases through identification of small carbohydrate inhibitors and mucus cell-specific promoter. ..
  3. Fatty acid related regulation of enteric infectious disease
    FREDRICK JON KULL; Fiscal Year: 2012
    ..confirmed using electrophoretic mobility shift assays (EMSAs), an NMR-based ligand binding assay, and site directed mutagenesis. Preliminary analysis has indicated that a number of pathogenic bacteria, including several types of ..
  4. FOXP3-microRNA146-NFkB Axis in Tumor Suppression
    Lizhong Wang; Fiscal Year: 2013
    ..abstract_text> ..
  5. Microsomal Cytochromes P450 and their Interactions with their Redox Partners
    Lucy A Waskell; Fiscal Year: 2013
  6. Neuropilin and semaphorin, anti-angiogenesis activities and mechanisms
    Michael Klagsbrun; Fiscal Year: 2009
    ..abstract_text> ..
  7. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
  8. Delineation of the molecular mechanisms underlying group A Streptococcus virulenc
    Paul Sumby; Fiscal Year: 2013
    ..Public health may be enhanced through the long-term goal of translating knowledge of FASX regulatory pathways into new treatment and/or preventative regimes based upon the inhibition of these pathways by novel antimicrobial agents. ..
  9. ANP Receptor: Molecular approach of signaling mechanisms
    Kailash N Pandey; Fiscal Year: 2013
    ..Ultimately, this knowledge should yield new therapeutic molecular targets for the diagnosis, control, and treatment of hypertension and cardiovascular diseases. ..
  10. Identifying Key Structural Elements in the Activation of the Arp2/3 Complex
    Patricia A Khuu; Fiscal Year: 2013
    ..Arp2/3 is also involved in metastasis as it is required in the formation of cellular structures such as lamellipodia of migrating cells and invadopodia of cancers cells [5, 6]. ..
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..PERFORMANCE SITE(S) (organization, city, state) University of California, Irvine, CA 92697, USA REVISED ABSTRACT SECTION ..
  12. Biosynthesis of Microbial Isoprenoids
    David E Cane; Fiscal Year: 2013
  13. Biosynthetic Protein Models of Heme-copper Oxidases and Nitric Oxide Reductases
    Yi Lu; Fiscal Year: 2013
    ..Therefore the work will make important contributions to healthcare, as it will provide a molecular basis for understanding two enzymes important to human health. ..
  14. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2013
  15. Transcriptional regulation of proteinuria
    SUMANT SINGH CHUGH; Fiscal Year: 2011
    ..of ZHX3 to the COL4A3 promoter will be studied by a combination of chromatin immunoprecipitation and site directed mutagenesis. Next, the influence of ZHX3 and interacting partners on the promoter activity of selected genes will be ..
  16. Regulation of the Expression of G[alpha]i2 by Reactive Oxygen Species
    Ifeanyi J Arinze; Fiscal Year: 2012
  17. Influence of Heme on Hepatic Cytochrome P450 Turnover
    Maria Almira Correia; Fiscal Year: 2013
    ..Moreover, such global alterations of hepatic P450 turnover would also rationalize the impaired drug clearance clinically observed in porphyric patients. ..
  18. Thrombospondin 4 A1
    JOHN W LAWLER; Fiscal Year: 2010
    ..The data from these studies will provide key insights into the function of the signature domain of COMP in terms of its interactions with various proteins, PGs and cells. ..
  19. Dopamine Transporter Structure and Function
    Christopher K Surratt; Fiscal Year: 2010
    Maria Almira Correia; Fiscal Year: 2013
    Jeffrey A Simon; Fiscal Year: 2012
    ..This research will advance basic understanding of gene regulatory mechanisms and provide knowledge that could impact stem cell applications in medicine and development of anti-cancer strategies. ..
    JAMES CARLTON GARRISON; Fiscal Year: 2010
    ..Lipin is phosphorylated in response to insulin. In AIM 1 a plan involving peptide mapping, site directed mutagenesis, and mass spectrometry is presented to determine the sites of phosphorylation...
  23. The role fo the TPP1 peotein in telomerase function and cancer cell survival
    Jayakrishnan Nandakumar; Fiscal Year: 2013
    ..I believe that the knowledge and experience I have gained thus far will greatly assist in the successful completion of the aims of the K99/R00 proposal in a timely fashion. ..
  24. Melanopsin Signal Transduction Studied by FTIR Spectroscopy
    Kenneth J Rothschild; Fiscal Year: 2012
  25. Novel High Affinity and Long-Acting Bovine FSH Analogs for Veterinary Superovulat
    BRUCE DALE WEINTRAUB; Fiscal Year: 2012
  26. Mechanisms regulating SR Ca2+ ATPase in the Atria
    Muthu Periasamy; Fiscal Year: 2012
    ..The role of SLN phosphorylation and its interaction with SERCA pump will be assessed using site directed mutagenesis, and adenoviral gene transfer into cardiac myocytes...
  27. Phospholemman and Cardiac Contracility
    Joseph Y Cheung; Fiscal Year: 2013
    ..In addition, the exact molecular site in sodium-calcium exchanger interacting with phospholemman will be mapped out by mutagenesis. ..
    William A Catterall; Fiscal Year: 2013
    ..This basic science information will be essential to understand and treat periodic paralysis, epilepsy, chronic pain, and cardiac arrhythmia. ..
  29. Mechanisms of assembly of photoreceptor G protein complexes
    Barry M Willardson; Fiscal Year: 2013
    ..An understanding of the way these protein complexes are brought together is necessary to develop treatments that would allow the complexes to assemble and function despite the mutations. ..
  30. Ligand Interaction of Glucagon Receptor by Structural and Functional Analyses
    FAI YIU SIU; Fiscal Year: 2012
  31. Coronavirus RNA Replication
    DAVID ALVIN BRIAN; Fiscal Year: 2012
    ..Knowing in detail what molecular interactions lead to coronavirus replication and recombination, the focus of this proposal, are essential for the development of stable and safe recombinant vaccines and the design of anti-viral drugs. ..
  32. Biophysics of Drug Interactions with Viral Episomes
    James K Bashkin; Fiscal Year: 2013
  33. Nonheme Diiron Centers and the Biological Oxidation of Hydrocarbons
    Stephen J Lippard; Fiscal Year: 2013
    ..The ability of these hydrocarbon-consuming "superbugs" to degrade chlorinated hydrocarbons has led to their application in the bioremediation of industrial wastewater, decontamination of seawater, and removal of soil pollutants. ..
  34. Regulation of mitochondrial metabolism by lysine acetylation
    Eric S Goetzman; Fiscal Year: 2013
  35. Molecular mechanism of apolipoprotein binding to lipopolysaccharides
    PAUL MICHIEL WEERS; Fiscal Year: 2013
    ..The proposed research aims to understand the molecular basis of the protective role of apolipoproteins, thereby providing a foundation for improving the treatment of bacterial sepsis. ..
  36. Separation-of-function Mutants to Study the Biological Significance of Telomerase
    Jayakrishnan Nandakumar; Fiscal Year: 2012
    ..From this study, it will be possible to understand how TPP1 stimulates telomerase to full potency in cancer cells, and the knowledge gained may pave the path to the design of a new generation of anti-cancer drugs. ..
  37. Meiosis, SUMOylation and the ZIP3 Protein: Parallel Studies in Mouse and Yeast.
    Neil Hunter; Fiscal Year: 2012
    ..Defects in these processes are linked to human infertility, miscarriage and genetic diseases, particularly cancer. A greater understanding of their mechanism and regulation will help us better understand the etiology of these diseases. ..
  38. Molecular mechanism of regulation of mI(CAT) in intestinal smooth muscle cells
    Michael X Zhu; Fiscal Year: 2012
    ..This will shed light on the pathogenesis and new treatment of a wide range of human diseases caused by smooth muscle dysfunctions, such as inflammatory bowel disease, irritable bowel syndrome, and urge incontinence. ..
  39. Redox Regulation of Kv Channels
    SRINIVAS TIPPARAJU; Fiscal Year: 2013
    ..These findings could provide insights into the development of new therapeutic interventions for the treatment and management of myocardial ischemic injury. ..
  40. Problems in Membrane Protein Crystallography: Hetero-Oligomeric Cytochrome b6f
    William A Cramer; Fiscal Year: 2012
    ..Via the membrane, the set of energy-transducing proteins determines the level of energy and its regulation in the human cell. ..
  41. Polymorphisms of estrogen-metabolizing genes in kidney cancer
    Yuichiro Tanaka; Fiscal Year: 2013
    ..Such information can lead to the identification of Veterans with higher risk for RCC. Proposed research may also lead to implications for possible therapy for RCC. ..
  42. The influenza A virus nucleoprotein: structure and function
    Yizhi Jane Tao; Fiscal Year: 2012
    ..The aim of this grant is to elucidate the molecular mechanism and biological significance of several key activities of the influenza A virus nucleoprotein and to discover how such activities can be exploited for antiviral development. ..
  43. Cell wall synthesis enzymes and beta-lactam resistance in Enterococcus faecium
    Louis B Rice; Fiscal Year: 2013
    ..They will also enhance our understanding of cell wall synthesis mechanisms in Gram-positive cocci and reveal promising new targets for antibacterial therapy. ..
  44. Physiology and Biophysics of Cardiac Slo2.1 Channels
    Alexey V Zaitsev; Fiscal Year: 2012
    ..These electrical gradients are highly relevant to the outcomes of cardiac defibrillation and resuscitation of individuals who have experienced sudden cardiac arrest. ..
  45. Novel Strategies for Treatment of Myeloproliferative Disorders
    Roya Khosravi-Far; Fiscal Year: 2012
    ..abstract_text> ..
  46. The mechanism of mRNA recruitment to the human ribosome.
    Christopher S Fraser; Fiscal Year: 2013
    ..An understanding of the mechanism and regulation of protein synthesis will therefore help us better understand this disease. ..
  47. Structure and Specificity in Metal Ion Homeostasis
    Amy C Rosenzweig; Fiscal Year: 2013
    ..Taken together, this body of work will address what is currently a huge gap in understanding of metal homeostasis. ..
  48. P63/IGFBP3/BCL2 Control of Corneal Epithelial Homeostasis
    Danielle M Robertson; Fiscal Year: 2011
  49. Study of the HFE Transferrin Receptor interaction in mammalian iron homeostasis
    Paul Schmidt; Fiscal Year: 2010
    ..Most importantly, this award will assist in the transition of the candidate to become a fully independent investigator in the field of iron metabolism. ..
  50. Structure/Function of Steroid Transforming AKR's
    Trevor M Penning; Fiscal Year: 2011
    ..This application will establish whether these genetic changes result in abnormal bile-acid production and are causal in these deficiencies. ..
  51. Interaction of thrombospondin-1 with alpha9beta1 integrin in glioma angiogenesis
    Cezary Marcinkiewicz; Fiscal Year: 2012
    ..Investigation of this receptor may be beneficial for cancer as well as for cardiovascular disease having patients, because regulation of vascularization process is important in these pathologies. ..
  52. Defining the role of Amot lipid binding in cellular proliferation and migration
    ANN CAROL KIMBLE-HILL; Fiscal Year: 2013
    ..Aim 1 is designed to use targeted site directed mutagenesis as a means to measure direct contact and insertion of ACCH tyrosines with synthetic membrane ..
    Hermann Steller; Fiscal Year: 2012
    ..Therefore, this project will have profound implications for both basic science and medicine. ..
  54. Regulation of orofacial ectodermal polarity by the CLP protein, IRF6
    EMILY YIN CHU; Fiscal Year: 2013
    ..With strong institutional support from the University of Washington and excellent mentorship, we are confident that this F30 award will aid in the basic sciences and clinical training required to be a successful clinician scientist. ..
  55. Cloning and Analysis of a Gamete Fusion Gene
    CHARLENE FOREST; Fiscal Year: 2009
    ..Future experiments may also involve site directed mutagenesis of the BAC sequences to allow further mapping of the protein's functional domains as well as real ..
  56. Low-affinity aryl hydrocarbon receptors in the frog Xenopus laevis
    Wade H Powell; Fiscal Year: 2010
    ..It will also aid in the understanding of important differences between frogs and humans as they interpret toxicology studies using frog embryos as a model system for measuring the effects of chemicals and environmental samples. ..
    ANTHONY PEGG; Fiscal Year: 2009
    ..abstract_text> ..
  58. Reactivity epitopes of ribonuclease III substrates
    ALLEN WHITALL NICHOLSON; Fiscal Year: 2010
  59. Structure-Function of the Shigella dysenteriae heme uptake operon (shu)
    Angela Wilks; Fiscal Year: 2012
    ..Heme utilization by S. dysenteriae is required for virulence and characterization of heme uptake and metabolism may provide novel therapeutic targets for drug development. ..
    PETER J TONTONOZ; Fiscal Year: 2013
    ..We will also generate and analyze lesion formation in Idol-/- human apoBTg mice. ..
  61. Focal Adhesion Kinase - Tumor Biology and Therapeutics
    William G Cance; Fiscal Year: 2013
    ..Thus, this application will provide novel molecular cancer therapeutics that target the focal adhesion kinase. ..
  62. Alternative Splicing in Regulation of Cholesterol Synthesis and Uptake
    Marisa Wong Medina; Fiscal Year: 2013
    ..SNP functionality will be confirmed by site directed mutagenesis of mini-gene constructs (Aim 3)...
    Chang An Yu; Fiscal Year: 2009
    ..compound activated by pulse laser;and by probing the nature of the intra-molecularpath of QH2 in QCR by site directed mutagenesis;(C) to synthesize Q-derivatives and inhibitors for protein:Q interaction studies;(D) to elucidate ..
    George Sachs; Fiscal Year: 2009
    ..The results of the proposed research will further improve the agents used for the treatment of acid-related diseases and also our knowledge of the ATPase and cellular events involved in regulation of its activity. ..
  65. Monoamine Transporter Structure-Function Studies
    CHRISTOPHER SURRATT; Fiscal Year: 2007
    ..unreadable] [unreadable]..
    Joseph Glorioso; Fiscal Year: 2000
    ..Differences in nucleosome arrangement will be analyzed by a nuclease sensitivity assay. Differences in the CpG sequence methylation will be analyzed. ..