ligands

Summary

Summary: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)

Top Publications

  1. ncbi Inference of macromolecular assemblies from crystalline state
    Evgeny Krissinel
    European Bioinformatics Institute, Genome Campus, Hinxton, Cambridge CB10 1SD, UK
    J Mol Biol 372:774-97. 2007
  2. ncbi Coot: model-building tools for molecular graphics
    Paul Emsley
    York Structural Biology Laboratory, University of York, Heslington, York YO10 5YW, England
    Acta Crystallogr D Biol Crystallogr 60:2126-32. 2004
  3. pmc AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading
    Oleg Trott
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA
    J Comput Chem 31:455-61. 2010
  4. pmc AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
    Garrett M Morris
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Comput Chem 30:2785-91. 2009
  5. ncbi Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
    Richard A Friesner
    Department of Chemistry, Columbia University, New York, New York 10036, USA
    J Med Chem 47:1739-49. 2004
  6. ncbi Notch signaling: cell fate control and signal integration in development
    S Artavanis-Tsakonas
    Massachusetts General Hospital Cancer Center, Department of Cell Biology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Science 284:770-6. 1999
  7. pmc High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor
    Vadim Cherezov
    Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
    Science 318:1258-65. 2007
  8. pmc Structure of a nanobody-stabilized active state of the β(2) adrenoceptor
    Søren G F Rasmussen
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, California 94305, USA
    Nature 469:175-80. 2011
  9. ncbi Toll-like receptor signalling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Rev Immunol 4:499-511. 2004
  10. pmc PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations
    Todd J Dolinsky
    Department of Biochemistry and Molecular Biophysics, Center for Computational Biology, Washington University in St Louis, 700 S Euclid Ave, Campus Box 8036, St Louis, MO 63110, USA
    Nucleic Acids Res 35:W522-5. 2007

Research Grants

Detail Information

Publications353 found, 100 shown here

  1. ncbi Inference of macromolecular assemblies from crystalline state
    Evgeny Krissinel
    European Bioinformatics Institute, Genome Campus, Hinxton, Cambridge CB10 1SD, UK
    J Mol Biol 372:774-97. 2007
    ..The method is implemented as a public WWW service...
  2. ncbi Coot: model-building tools for molecular graphics
    Paul Emsley
    York Structural Biology Laboratory, University of York, Heslington, York YO10 5YW, England
    Acta Crystallogr D Biol Crystallogr 60:2126-32. 2004
    ..The map-fitting tools are available as a stand-alone package, distributed as 'Coot'...
  3. pmc AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading
    Oleg Trott
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA
    J Comput Chem 31:455-61. 2010
    ..Further speed-up is achieved from parallelism, by using multithreading on multicore machines. AutoDock Vina automatically calculates the grid maps and clusters the results in a way transparent to the user...
  4. pmc AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
    Garrett M Morris
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Comput Chem 30:2785-91. 2009
    ..We also report its utility in analysis of covalently bound ligands, using both a grid-based docking method and a modification of the flexible sidechain technique.
  5. ncbi Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
    Richard A Friesner
    Department of Chemistry, Columbia University, New York, New York 10036, USA
    J Med Chem 47:1739-49. 2004
    Unlike other methods for docking ligands to the rigid 3D structure of a known protein receptor, Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand...
  6. ncbi Notch signaling: cell fate control and signal integration in development
    S Artavanis-Tsakonas
    Massachusetts General Hospital Cancer Center, Department of Cell Biology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Science 284:770-6. 1999
    ..Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis...
  7. pmc High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor
    Vadim Cherezov
    Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
    Science 318:1258-65. 2007
    ....
  8. pmc Structure of a nanobody-stabilized active state of the β(2) adrenoceptor
    Søren G F Rasmussen
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, California 94305, USA
    Nature 469:175-80. 2011
    ..coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs...
  9. ncbi Toll-like receptor signalling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Rev Immunol 4:499-511. 2004
  10. pmc PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations
    Todd J Dolinsky
    Department of Biochemistry and Molecular Biophysics, Center for Computational Biology, Washington University in St Louis, 700 S Euclid Ave, Campus Box 8036, St Louis, MO 63110, USA
    Nucleic Acids Res 35:W522-5. 2007
    ..Methods for calculating pK(a) values, binding constants of ligands, and changes in protein stability are readily available, but often the limiting step in computational biology is ..
  11. ncbi Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes
    Richard A Friesner
    Department of Chemistry, Columbia University, New York, New York 10027, USA
    J Med Chem 49:6177-96. 2006
    ..26 and 1.73 kcal/mol over all and well-docked ligands, respectively) and to yield quality enrichments for a set of fifteen screens of pharmaceutical importance...
  12. pmc Predicting new molecular targets for known drugs
    Michael J Keiser
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, San Francisco, California 94143 2550, USA
    Nature 462:175-81. 2009
    ..Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations...
  13. ncbi Chemokines: a new classification system and their role in immunity
    A Zlotnik
    DNAX Research Institute, Palo Alto, California 94304, USA
    Immunity 12:121-7. 2000
  14. ncbi PRODRG: a tool for high-throughput crystallography of protein-ligand complexes
    Alexander W Schuttelkopf
    Division of Biological Chemistry and Molecular Microbiology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dow Street, DD1 5EH, Scotland
    Acta Crystallogr D Biol Crystallogr 60:1355-63. 2004
    ..However, tests with distorted starting coordinates show that PRODRG topologies perform better, both in terms of ligand geometry and of crystallographic R factors...
  15. pmc The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist
    Veli Pekka Jaakola
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037 USA
    Science 322:1211-7. 2008
    ....
  16. ncbi The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability
    Frank H Niesen
    Structural Genomics Consortium, Botnar Research Centre, Oxford University, Oxford, UK
    Nat Protoc 2:2212-21. 2007
    ..scanning fluorimetry (DSF) is a rapid and inexpensive screening method to identify low-molecular-weight ligands that bind and stabilize purified proteins...
  17. ncbi Toll-like receptors and innate immunity
    R Medzhitov
    Section of Immunobiology, Yale University School Medicine, and Howard Hughes Medical Institute, New Haven, Connecticut 06520, USA
    Nat Rev Immunol 1:135-45. 2001
    ..Recognition of microbial products by Toll-like receptors expressed on dendritic cells triggers functional maturation of dendritic cells and leads to initiation of antigen-specific adaptive immune responses...
  18. ncbi PD-1 and its ligands in tolerance and immunity
    Mary E Keir
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115 5727, USA
    Annu Rev Immunol 26:677-704. 2008
    Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology...
  19. ncbi NK cell recognition
    Lewis L Lanier
    Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco School of Medicine, San Francisco, California 94143 0414, USA
    Annu Rev Immunol 23:225-74. 2005
    ..Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition...
  20. ncbi Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening
    Thomas A Halgren
    Schrodinger, L L C, 120 W 45th Street, New York, New York 10036, USA
    J Med Chem 47:1750-9. 2004
    ..To make the database screens as realistic as possible, the screens use sets of "druglike" decoy ligands that have been selected to be representative of what we believe is likely to be found in the compound collection ..
  21. pmc The role of dynamic conformational ensembles in biomolecular recognition
    David D Boehr
    Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA
    Nat Chem Biol 5:789-96. 2009
    ....
  22. pmc R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling
    Kendra S Carmon
    Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 108:11452-7. 2011
    ..The findings provide a basis for stem cell-specific effects of Wnt/β-catenin signaling and for the broad range of functions LGR4, LGR5, and the R-spondins have in normal and malignant growth...
  23. pmc Structure of the human histamine H1 receptor complex with doxepin
    Tatsuro Shimamura
    Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Kyoto 606 8501, Japan
    Nature 475:65-70. 2011
    ..Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R...
  24. pmc Structure of a beta1-adrenergic G-protein-coupled receptor
    Tony Warne
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nature 454:486-91. 2008
    ....
  25. ncbi Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites
    Alasdair T R Laurie
    School of Biochemistry and Microbiology, University of Leeds, UK
    Bioinformatics 21:1908-16. 2005
    ..Energetically favourable probe sites are clustered according to their spatial proximity and clusters are then ranked according to the sum of interaction energies for sites within each cluster...
  26. pmc A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells
    Antoine Claessens
    Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Proc Natl Acad Sci U S A 109:E1772-81. 2012
    ..58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria...
  27. ncbi The receptor for the cytotoxic ligand TRAIL
    G Pan
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 276:111-3. 1997
    ..Thus, the DR4-TRAIL axis defines another receptor-ligand pair involved in regulating cell suicide and tissue homeostasis...
  28. pmc Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation
    G J Freeman
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Exp Med 192:1027-34. 2000
    ..PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation...
  29. ncbi Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta
    G G Kuiper
    Center for Biotechnology, Karolinska Institute, Huddinge, Sweden
    Endocrinology 138:863-70. 1997
    ..The described differences between the ER subtypes in relative ligand binding affinity and tissue distribution could contribute to the selective action of ER agonists and antagonists in different tissues...
  30. pmc BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities
    Tiqing Liu
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA
    Nucleic Acids Res 35:D198-201. 2007
    ..for 110 protein targets including isoforms and mutational variants, and approximately 11,000 small molecule ligands. The data are extracted from the scientific literature, data collection focusing on proteins that are drug-..
  31. pmc Dermal β-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation
    Demeng Chen
    Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA
    Development 139:1522-33. 2012
    ..We show in mice that epidermal Wnt ligands are required for uniform dermal Wnt signaling/β-catenin activity and regulate fibroblast cell proliferation and ..
  32. ncbi CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides
    T Kawano
    CREST Core Research for Evolutional Science and Technology Project, Japan Science and Technology Corporation JST, 1 8 1 Inohana, Chuo, Chiba 260, Japan
    Science 278:1626-9. 1997
    ..Thus, this lymphocyte shares distinct recognition systems with either T or NK cells...
  33. ncbi Improved protein-ligand docking using GOLD
    Marcel L Verdonk
    Astex Technology, Ltd, Cambridge, United Kingdom
    Proteins 52:609-23. 2003
    ..were made for a "clean" set of 224 protein-ligand complexes, and for two subsets of this set, one for which the ligands are "drug-like," the other for which they are "fragment-like...
  34. pmc The RCSB Protein Data Bank: redesigned web site and web services
    Peter W Rose
    San Diego Supercomputer Center, University of California San Diego, 9500 Gilman Drive, Mailcode 0743, La Jolla, CA 92093 0743, USA
    Nucleic Acids Res 39:D392-401. 2011
    ..These improvements enable a range of new possibilities to analyze and understand structure data. The next generation of the RCSB PDB web site, as described here, provides a rich resource for research and education...
  35. pmc International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂
    R G Pertwee
    School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK
    Pharmacol Rev 62:588-631. 2010
    There are at least two types of cannabinoid receptors (CB(1) and CB(2)). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ(9)-tetrahydrocannabinol, numerous synthetic compounds, and endogenous ..
  36. pmc Integrin ligands at a glance
    Jonathan D Humphries
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
    J Cell Sci 119:3901-3. 2006
  37. ncbi The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes
    Karl Balabanian
    Unite d Immunologie Virale, Institut Pasteur, 75015 Paris, France
    J Biol Chem 280:35760-6. 2005
    ..In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12...
  38. pmc Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation
    Guillaume Lebon
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nature 474:521-5. 2011
    ....
  39. ncbi The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities
    Y Yarden
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Eur J Cancer 37:S3-8. 2001
    ..In humans, more than 30 ligands and the EGFR family of four receptors lie at the head of a complex, multi-layered signal-transduction network...
  40. pmc Carbohydrate-binding modules: fine-tuning polysaccharide recognition
    Alisdair B Boraston
    Biochemistry and Microbiology, University of Victoria, PO Box 3055 STN CSC, Victoria, BC, Canada V8W 3P6
    Biochem J 382:769-81. 2004
    ..The present review summarizes the impact structural biology has had on our understanding of the mechanisms by which CBMs bind to their target ligands.
  41. pmc Teaching old receptors new tricks: biasing seven-transmembrane receptors
    Sudarshan Rajagopal
    Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina 27710, USA
    Nat Rev Drug Discov 9:373-86. 2010
    ..has distinct biochemical and functional consequences from those mediated by G proteins, and several biased ligands and receptors have been identified that preferentially signal through either G protein- or beta-arrestin-mediated ..
  42. ncbi LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites
    C M Venkatachalam
    Accelrys Inc, 9685 Scranton Road, San Diego, CA 92121, USA
    J Mol Graph Model 21:289-307. 2003
    We present a new shape-based method, LigandFit, for accurately docking ligands into protein active sites. The method employs a cavity detection algorithm for detecting invaginations in the protein as candidate active site regions...
  43. pmc Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity
    Eric M Kofoed
    Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Nature 477:592-5. 2011
    ..in mice that different NAIP paralogues determine the specificity of the NLRC4 inflammasome for distinct bacterial ligands. In particular, we found that activation of endogenous NLRC4 by bacterial PrgJ requires NAIP2, a previously ..
  44. pmc 3DLigandSite: predicting ligand-binding sites using similar structures
    Mark N Wass
    Structural Bioinformatics Group, Centre for Bioinformatics, Imperial College London, London, SW7 2AZ, UK
    Nucleic Acids Res 38:W469-73. 2010
    ..b>Ligands bound to structures similar to the query are superimposed onto the model and used to predict the binding site...
  45. pmc Crystal structure of the µ-opioid receptor bound to a morphinan antagonist
    Aashish Manglik
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 485:321-6. 2012
    ..These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction...
  46. ncbi Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis
    Seth Rakoff-Nahoum
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 118:229-41. 2004
    Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms...
  47. pmc Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response
    Brooke M Gardner
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
    Science 333:1891-4. 2011
    ..Peptide binding caused Ire1 cLD oligomerization in vitro, suggesting that direct binding to unfolded proteins activates the UPR...
  48. ncbi Identification of a nuclear receptor for bile acids
    M Makishima
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9050, USA
    Science 284:1362-5. 1999
    ..Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor...
  49. pmc DNA binding site sequence directs glucocorticoid receptor structure and activity
    Sebastiaan H Meijsing
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
    Science 324:407-10. 2009
    ..We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes...
  50. ncbi HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection
    Salim I Khakoo
    Liver Group, Division of Infection, Inflammation, and Repair, Southampton University, Southampton 5016 6YD, UK
    Science 305:872-4. 2004
    ..The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV...
  51. ncbi Ligand efficiency: a useful metric for lead selection
    Andrew L Hopkins
    Drug Discov Today 9:430-1. 2004
  52. ncbi PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein
    N Maeda
    Department of Internal Medicine and Molecular Science (B5, Graduate School of Medicine, Osaka University, Osaka, Japan
    Diabetes 50:2094-9. 2001
    ..In this study, we demonstrate the inducing effects of thiazolidinediones (TZDs), which are synthetic PPARgamma ligands, on the expression and secretion of adiponectin in humans and rodents in vivo and in vitro...
  53. ncbi Very fast prediction and rationalization of pKa values for protein-ligand complexes
    Delphine C Bas
    Equipe de Chimie et Biochimie Theoriques, UMR 7565 CNRS, Universite Henri Poincare, Nancy I, Boulevard des Aiguillettes BP 239, 54506 Vandoeuvre les Nancy Cedex, France
    Proteins 73:765-83. 2008
    ..of the pK(a) values of ionizable residues in proteins is extended to include the effect of non-proteinaceous ligands on protein pK(a) values as well as predict the change in pK(a) values of ionizable groups on the ligand itself...
  54. ncbi MolDock: a new technique for high-accuracy molecular docking
    René Thomsen
    Molegro ApS, Hoegh Guldbergs Gade 10, Bldg 1090, DK 8000 Aarhus C, Denmark
    J Med Chem 49:3315-21. 2006
    ..The docking accuracy of MolDock has been evaluated by docking flexible ligands to 77 protein targets. MolDock was able to identify the correct binding mode of 87% of the complexes...
  55. pmc Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist
    Kazuko Haga
    Department of Life Science, Faculty of Science, Gakushuin University, Mejiro 1 5 1, Tokyo 171 8588, Japan
    Nature 482:547-51. 2012
    ..interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor ..
  56. pmc Conformer generation with OMEGA: algorithm and validation using high quality structures from the Protein Databank and Cambridge Structural Database
    Paul C D Hawkins
    OpenEye Scientific Software, 9 Bisbee Court, Suite D, Santa Fe, New Mexico 87508, USA
    J Chem Inf Model 50:572-84. 2010
    ..OMEGA is found to perform very well in reproducing the crystallographic conformations from both these data sets using two complementary metrics of success...
  57. ncbi GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function
    Daniel M Rosenbaum
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Science 318:1266-73. 2007
    ..Amino acids known to regulate receptor function are linked through packing interactions and a network of hydrogen bonds, suggesting a conformational pathway from the ligand-binding pocket to regions that interact with G proteins...
  58. ncbi Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Science 301:640-3. 2003
    ..Furthermore, inflammatory cytokine production in response to the TLR4 ligand, but not to other TLR ligands, was severely impaired in TRIF-deficient macrophages...
  59. ncbi Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer
    Jin Young Kang
    Department of Chemistry, KAIST, Daejon, 305 701, Korea
    Immunity 31:873-84. 2009
    ..The structures of the TLR2-lipoteichoic acid and the TLR2-PE-DTPA complexes demonstrate that a precise interaction pattern of the head group is essential for a robust immune response by TLR2 heterodimers...
  60. ncbi Relating protein pharmacology by ligand chemistry
    Michael J Keiser
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco California 94143 2550, USA
    Nat Biotechnol 25:197-206. 2007
    ..complementary technique that quantitatively groups and relates proteins based on the chemical similarity of their ligands. We began with 65,000 ligands annotated into sets for hundreds of drug targets...
  61. ncbi Detailed analysis of grid-based molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm
    Guosheng Wu
    Eli Lilly and Company, Lilly Research Laboratories, DC 1513, Indianapolis, Indiana 46285, USA
    J Comput Chem 24:1549-62. 2003
    ..In these docking studies, the protein is kept rigid while the ligands are treated as fully flexible and a final minimization step is used to refine the docked poses...
  62. ncbi Use of defined TLR ligands as adjuvants within human vaccines
    Malcolm S Duthie
    Infectious Disease Research Institute, Seattle, WA, USA
    Immunol Rev 239:178-96. 2011
    ..first generation vaccines, as well as rapid advances in developing defined vaccines containing Toll-like receptor ligands (TLRLs), indicate that an expanded number of safe and effective vaccines containing such molecules will be ..
  63. ncbi Mechanisms of estrogen action
    S Nilsson
    KaroBio AB and Department of Biosciences, Karolinska Institute, Novum, Huddinge, Sweden
    Physiol Rev 81:1535-65. 2001
    ..have revealed much about how ligand binding influences receptor conformation and how this conformation influences interaction of the receptor with coactivators or corepressors and hence determines cellular response to ligands.
  64. pmc Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity
    Till Maurer
    Structural Biology, Genentech, Inc, One DNA Way, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 109:5299-304. 2012
    ..The discovery of a small-molecule binding pocket on Ras with functional significance provides a new direction in the search of therapeutically effective inhibitors of the Ras oncoprotein...
  65. pmc Automated design of ligands to polypharmacological profiles
    Jérémy Besnard
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Nature 492:215-20. 2012
    ..Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets...
  66. pmc Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5
    Jang Hyun Choi
    Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 466:451-6. 2010
    ..The phosphorylation of PPARgamma by Cdk5 is blocked by anti-diabetic PPARgamma ligands, such as rosiglitazone and MRL24...
  67. pmc Benchmarking sets for molecular docking
    Niu Huang
    Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143 2550, USA
    J Med Chem 49:6789-801. 2006
    ..To avoid bias, decoys should resemble ligands physically, so that enrichment is not simply a separation of gross features, yet be chemically distinct from them,..
  68. ncbi Apoptosis by death factor
    S Nagata
    Department of Genetics, Osaka University Medical School, Japan
    Cell 88:355-65. 1997
  69. ncbi Novel procedure for modeling ligand/receptor induced fit effects
    Woody Sherman
    Schrodinger, Inc, New York, New York 10036, USA
    J Med Chem 49:534-53. 2006
    ..4 A; the RMSD is < or =1.8 A for 18 of the cases. For the three cases with RMSDs greater than 1.8 A, the core of the ligand is properly docked and all key protein/ligand interactions are captured...
  70. ncbi Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals
    Michael S Denison
    Department of Environmental Toxicology, University of California, Davis, California 95616, USA
    Annu Rev Pharmacol Toxicol 43:309-34. 2003
    ..In addition to synthetic and environmental chemicals, numerous naturally occurring dietary and endogenous AhR ligands have also been identified...
  71. ncbi LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters
    Gerhard Wolber
    Inte Ligand GmbH, Mariahilferstrasse 74B 11, A 1070 Vienna, Austria
    J Chem Inf Model 45:160-9. 2005
    From the historically grown archive of protein-ligand complexes in the Protein Data Bank small organic ligands are extracted and interpreted in terms of their chemical characteristics and features...
  72. pmc Structure of an agonist-bound human A2A adenosine receptor
    Fei Xu
    Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 332:322-7. 2011
    ..The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration...
  73. ncbi Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains
    Hideo Ogiso
    RIKEN Genomic Sciences Center, 1 7 22 Suehiro cho, Tsurumi, 230 0045, Yokohama, Kanagawa, Japan
    Cell 110:775-87. 2002
    ..The unique "receptor-mediated dimerization" was verified by EGFR mutagenesis...
  74. ncbi X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation
    Nicolas Bocquet
    Pasteur Institute, G5 Group of Channel Receptor, CNRS URA 2182
    Nature 457:111-4. 2009
    ..These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation...
  75. pmc The structural basis of agonist-induced activation in constitutively active rhodopsin
    Jörg Standfuss
    Paul Scherrer Institut, 5232 Villigen PSI, Switzerland
    Nature 471:656-60. 2011
    ..We thus show how an agonist ligand can activate its GPCR...
  76. ncbi The C-type lectin-like domain superfamily
    Alex N Zelensky
    Computational Proteomics and Therapy Design Group, John Curtin School of Medical Research, Australian National University, Canberra, Australia
    FEBS J 272:6179-217. 2005
    ..and evolutionarily flexible, and is involved in Ca2+-dependent carbohydrate binding and interaction with other ligands. This loop is completely absent in a subset of CTLDs, which we refer to as compact CTLDs; these include the Link/..
  77. ncbi Endogenous ligands of TLR2 and TLR4: agonists or assistants?
    Clett Erridge
    Department of Cardiovascular Sciences, Glenfield General Hospital, University of Leicester, Leicester, UK, LE3 9QP
    J Leukoc Biol 87:989-99. 2010
    ..However, since the discovery of their microbial ligands, many studies have provided evidence that host-derived molecules may also stimulate TLR2- or TLR4-dependent ..
  78. pmc The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor
    Tony Warne
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nature 469:241-4. 2011
    ..are G-protein-coupled receptors (GPCRs) that activate intracellular G proteins upon binding catecholamine agonist ligands such as adrenaline and noradrenaline...
  79. pmc CXCR3 ligands: redundant, collaborative and antagonistic functions
    Joanna R Groom
    Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Immunol Cell Biol 89:207-15. 2011
    ..CXCR3 is activated by three interferon (IFN)-γ-inducible ligands CXCL9 (monokine induced by gamma-interferon), CXCL10 (interferon-induced protein-10) and CXCL11 (interferon-..
  80. ncbi A semiempirical free energy force field with charge-based desolvation
    Ruth Huey
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA
    J Comput Chem 28:1145-52. 2007
    ..diverse protein-ligand complexes of known structure and binding energy, and tested on a set of 100 complexes of ligands with retroviral proteases...
  81. pmc Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer
    Rong Hu
    Department of Urology, Oncology, and Pathology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Cancer Res 69:16-22. 2009
    ..In addition, as expression markers for lethal PCa, these novel AR variants may be explored as potential biomarkers and therapeutic targets for advanced PCa...
  82. ncbi Soluble proteins in insect chemical communication
    P Pelosi
    Dipartimento di Chimica e Biotecnologie Agrarie, University of Pisa Italy, Agrarie via S Michele, 4, 56124, Pisa, Italy
    Cell Mol Life Sci 63:1658-76. 2006
    ..Here we review the structural properties of both classes of soluble proteins, their affinity to small ligands, and their expression in the different parts of the insect body and subcellular localisation...
  83. ncbi Bile acids: natural ligands for an orphan nuclear receptor
    D J Parks
    Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA
    Science 284:1365-8. 1999
    ..As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor ..
  84. ncbi Uncovering molecular mechanisms involved in activation of G protein-coupled receptors
    U Gether
    Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark
    Endocr Rev 21:90-113. 2000
    ....
  85. ncbi High-density miniaturized thermal shift assays as a general strategy for drug discovery
    M W Pantoliano
    Millennium Pharmaceuticals Inc, Cambridge, MA 02139, USA
    J Biomol Screen 6:429-40. 2001
    ....
  86. pmc Identification of a dendritic cell receptor that couples sensing of necrosis to immunity
    David Sancho
    Immunobiology Laboratory, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nature 458:899-903. 2009
    ..Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal dendritic-cell subset involved in regulating cross-priming to cell-associated antigens...
  87. pmc Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic
    Aaron A Thompson
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nature 485:395-9. 2012
    ..distinct pharmacology, featuring activation by the endogenous peptide N/OFQ, and unique selectivity for exogenous ligands. Here we report the crystal structure of human NOP, solved in complex with the peptide mimetic antagonist ..
  88. ncbi Crystal structure of the ligand-free G-protein-coupled receptor opsin
    Jung Hee Park
    Institut für Medizinische Physik und Biophysik CC2, Charite Universitatsmedizin Berlin, Chariteplatz 1, D 10117 Berlin, Germany
    Nature 454:183-7. 2008
    ..The opsin structure sheds new light on ligand binding to GPCRs and on GPCR activation...
  89. ncbi Identification of cavities on protein surface using multiple computational approaches for drug binding site prediction
    Zengming Zhang
    Systems Biology Division, Zhejiang California International Nanosystems Institute, Zhejiang University, 310029 Hangzhou, China
    Bioinformatics 27:2083-8. 2011
    ..In our previous work, MetaPocket, we have proved that it is possible to combine the results of many methods together to improve the prediction result...
  90. ncbi Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors
    Weihai He
    Tularik Inc, 1120 Veterans Boulevard, South San Francisco, California 94080, USA
    Nature 429:188-93. 2004
    ..Thus by acting as ligands for GPCRs, succinate and alpha-ketoglutarate are found to have unexpected signalling functions beyond their ..
  91. ncbi Spatial control of EGF receptor activation by reversible dimerization on living cells
    Inhee Chung
    Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 464:783-7. 2010
    ..Interestingly, dimers were enriched in the cell periphery in an actin- and receptor-expression-dependent fashion, resulting in a peripheral enhancement of EGF-induced signalling that may enable polarized responses to growth factors...
  92. pmc IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels
    Anthony J Harmar
    Centres for Cardiovascular Science and Neuroscience Research, The Queen s Medical Research Institute, Institute of Evolutionary Biology, Ashworth Labs, School of Informatics, University of Edinburgh, Edinburgh, UK
    Nucleic Acids Res 37:D680-5. 2009
    ..description of the genes and their functions, with information on protein structure and interactions, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g...
  93. ncbi Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation
    Veronika Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, Washington 98109, USA
    Nature 419:734-8. 2002
    Engagement of the NKG2D receptor by tumour-associated ligands may promote tumour rejection by stimulating innate and adaptive lymphocyte responses...
  94. ncbi PD-L2 is a second ligand for PD-1 and inhibits T cell activation
    Y Latchman
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Nat Immunol 2:261-8. 2001
    ..Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses...
  95. ncbi Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941
    Teemu T Junttila
    Research Oncology, Genentech, Inc, 1 DNA Way, Mailstop 72, South San Francisco, CA 94080, USA
    Cancer Cell 15:429-40. 2009
    ..A selective and potent PI3K inhibitor, GDC-0941, is highly efficacious both in combination with trastuzumab and in the treatment of trastuzumab-resistant cells and tumors...
  96. ncbi Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells
    O Mandelboim
    The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassha Medical School, Jerusalem, Israel
    Nature 409:1055-60. 2001
    ..NK cells also express triggering receptors that are specific for non-MHC ligands; but the nature of the ligands recognized on target cells is undefined...
  97. ncbi Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors
    J P Sheridan
    Department of Molecular Oncology, Genentech, South San Francisco, CA 94080 4918, USA
    Science 277:818-21. 1997
    ..DcR1 acted as a decoy receptor that inhibited TRAIL signaling. Thus, a cell surface mechanism exists for the regulation of cellular responsiveness to pro-apoptotic stimuli...
  98. ncbi Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand
    Jian Ping Xiong
    Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA
    Science 296:151-5. 2002
    The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown...
  99. ncbi The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54
    M Kotani
    Institut de Recherche Interdisciplinare en Biologie Humaine et Nucléaire I R I B H N, Brussels, Belgium
    J Biol Chem 276:34631-6. 2001
    ..Stimulation of oxytocin secretion after kisspeptin administration to rats confirmed this hypothesis...
  100. pmc Crystal structure of the extracellular segment of integrin alpha Vbeta3
    J P Xiong
    Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
    Science 294:339-45. 2001
    ..mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands. We have solved the crystal structure of the extracellular portion of integrin alphaVbeta3 at 3.1 A resolution...
  101. ncbi Docking ligands into flexible and solvated macromolecules. 4. Are popular scoring functions accurate for this class of proteins?
    Pablo Englebienne
    Department of Chemistry, McGill University, 801 Sherbrooke St W, Montreal, Quebec, Canada H3A 2K6
    J Chem Inf Model 49:1568-80. 2009
    ..To this effect, we developed two sets of protein/ligand complexes made up of ligands cross-docked or cocrystallized with a large variety of proteins, featuring bridging water molecules and ..

Research Grants76

  1. Developmental analysis of SELCT proteins
    ANNE CHURCH HART; Fiscal Year: 2010
    ..Notch receptors bind extracellular ligands (e.g. Delta, Serrate and LAG-2) containing a conserved DSL domain that is critical for receptor activation...
  2. Sulfotransferases in the Synthesis of L-Selectin Ligands
    Steven D Rosen; Fiscal Year: 2010
    ..This step is mediated by L-selectin, a C-type lectin, which recognizes a set of carbohydrate-based ligands on HEVs. A function-blocking mAb called MECA-79 recognizes the same complex, referred to as PNAd...
  3. AGONISTS AND ANTAGONISTS OF VASOPRESSIN AND OXYTOCIN
    Maurice Manning; Fiscal Year: 2006
    ..2) To design high affinity radioiodinatable and fluorescent ligands for the putative VP vasodilating receptor. (3) To design specific antagonists of this receptor...
  4. Anti-Inflammatory Glycosaminoglycan Ethers for Treatment of Periodontitis
    JUSTIN RODNEY SAVAGE; Fiscal Year: 2011
    ..Sulfated glycosaminoglycans (GAGs, e.g., heparin) block ligation of RAGE by AGE and its other ligands. GAGs show other activities that could also be beneficial in treating gingivitis, including prevention of gram-..
  5. Pharmacogenetics of obesity and endocannabinergic modulation (POEM)
    Russell A Wilke; Fiscal Year: 2012
    ..The CB1 receptor has two endogenous ligands: N-arachidonylethanolamine (AEA) and 2-arachdionylglycerol (2-AG)...
  6. Effect of PPARy Ligands on Alcohol-Induced Alveolar Macrophage Oxidative Stress
    Samantha M Yeligar; Fiscal Year: 2013
    ..derangements can be reversed by treatment with peroxisome proliferator-activated receptor gamma (PPAR?) ligands, such as pioglitazone and rosiglitazone...
  7. T cell regulation by N-glycosylation
    Michael Demetriou; Fiscal Year: 2013
    ..galectin-3 binds the T cell receptor (TCR) and prevents spontaneous TCR oligomerization in the absence of antigen ligands. This in turn blocks recruitment of Nck, WASp, SLP-76 and CD4-Lck to TCR, F-actin remodeling and transfer of the ..
  8. Induction and maintenance of regulatory T cells
    Mitchell Kronenberg; Fiscal Year: 2013
    ..In Project 4 led by Dr. Croft, we will examine the lectins Galectins-3 and -9, which we have shown are novel ligands for the TNF family receptor 4-1 BB...
  9. Cellular &Molecular Defects in Human B Cell Development
    Charlotte Cunningham-Rundles; Fiscal Year: 2013
    ..of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and the function of its ligands and toll like receptor ligands (TLR) in B cell differentiation and maturation...
  10. Role of the Mammalian Siderophore in Cellular Iron Metabolism and Erythropoiesis
    Laxminarayana R Devireddy; Fiscal Year: 2012
    ..24p3 is a member of the lipocalin family a group of carrier proteins that bind and transport a variety of ligands and function in disparate biological processes ranging from vitamin delivery to apoptosis...
  11. Role of CD44 in experimental Multiple Sclerosis
    Mitzi Nagarkatti; Fiscal Year: 2013
    ..T cells express unique CD44v isoforms which promote their interactions with ECs at the BBB via specific ligands, such as hyaluronic acid (HA) and/or osteopontin (OPN)...
  12. Biology of IGFs in Bone
    Thomas L Clemens; Fiscal Year: 2013
    ..These functions were accomplished by the actions of multiple related ligands that activated a common transmembrane receptor protein...
  13. Tissue-specific delivery of probes by control of membrane trafficking of endoprot
    Blake Peterson; Fiscal Year: 2010
    ..The way that Nature solves this problem is through membrane trafficking;cell impermeable ligands such as the iron-carrying transferrin protein bind cognate receptors, in this case the transferrin receptor, that ..
  14. Structural Basis for Chemokine Function
    Brian F Volkman; Fiscal Year: 2013
    ..The chemokine SDF1 and other ligands for its receptor CXCR4 can block HIV-1 infection of T cells...
  15. PATHOPHYSIOLOGY OF THE ENDOTHELIUM
    Francis W Luscinskas; Fiscal Year: 2013
    ..In this amended renewal application, Project 1 will study the contribution of endothelial CD47 and its ligands Signal Regulatory Proteins and thrombospondin, as well as leukocyte CD47 dependent regulation of VLA-4 and LFA-1 ..
  16. Targeting CC-Chemokine Receptor 7 for the prevention of graft-versus-host disease
    JAMES M COGHILL; Fiscal Year: 2013
    ..work, we will use genetically engineered cell lines which generate a color signal in the presence of the natural ligands for CCR7: CCL19 and CCL21...
  17. Cell signaling as a leukemia biomarker
    JAMES WILLIAM JACOBBERGER; Fiscal Year: 2013
    ..Our specific aims are 1) to measure signaling for 2 ligands (Stem cell factor and Flt3-ligand) and 5 endpoints (Erk, Akt, S6, Stat3, and Stat5) on committed myeloid ..
  18. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The plant bioflavonoid, luteolin (L or LUT), and two synthetic ligands (BMHPC and ZN-2) interact with type II [3H]estradiol binding sites with high affinity (Kd" 5nM) and inhibit normal and malignant ..
  19. MOLECULAR MECHANISMS OF DIOXIN ACTION
    Alvaro Puga; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: The exposure of human populations to aryl hydrocarbon receptor organochlorinated ligands has been associated with a number of disease outcomes, including cancer, chloracne, cardiovascular disease, ..
  20. Anti-Inflammatory Glycosaminoglycan Ethers for Treatment of Periodontitis
    JUSTIN RODNEY SAVAGE; Fiscal Year: 2013
    ..block complement receptor-3 (CR3, also known as Mac-1), and block interaction of RAGE with its known important ligands, including AGEs, high mobility group box-1 protein (HMGB-1) and S100 calgranulins...
  21. Integrated signaling of eicosanoids in HSC formation and regeneration
    Trista E North; Fiscal Year: 2013
    ..The rationale for our work is that a detailed understanding of the impact of CB ligands on PGE2-mediated HSC growth and proliferation will enable targeted therapeutic approaches for the treatment of ..
  22. Impacts of surface receptors [Toll like receptor (TLRs) and Fc gamma receptors (F
    Collins Ouma; Fiscal Year: 2012
    ..TLRs are crucial components of the innate immune response to various microbial ligands and reactive host products...
  23. Regulation of NFkappaB activity by the Estrogen Receptor
    Kendall W Nettles; Fiscal Year: 2012
    ..Our hypothesis is that ER ligands that modulate NF-B induce a unique conformation of ER, facilitating association with gene-specific protein ..
  24. Mechanisms and Consequences of Reduced PPAR gamma in Pulmonary Hypertension
    C Michael Hart; Fiscal Year: 2013
    ..Unfortunately, these same PPARg ligands also cause significant side effects...
  25. Preclinical drug trial in mouse models of inflammation
    Kanneboyina Nagaraju; Fiscal Year: 2011
    ..Thus, ligands that preferentially induce the transrepression and not transactivation function of the GR are ideal for treating ..
  26. CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGS
    Stephen J Lippard; Fiscal Year: 2013
    ..Understanding the role of ligands on platinum in blocking transcription while eluding repair will guide the synthesis of new Pt drug candidates...
  27. Growth Hormone Regulation of SH2B1
    Christin Carter-Su; Fiscal Year: 2013
    ..strikingly similar to that of SH2B1-/- mice) is consistent with SH2B1 being a signaling molecule for multiple ligands, including growth hormone (GH), leptin, and insulin...
  28. Regulation of vaccine-induced anti-fungal T17 cells
    MARCEL WUETHRICH; Fiscal Year: 2013
    ..in vivo adoptive transfer system to delineate the signaling adaptors, pathogen recognition receptors, and fungal ligands that induce differentiation of naive antigen-specific CD4+ T- cells into protective T17 cells...
  29. BMP signaling in vertebrate development
    Ken W Y Cho; Fiscal Year: 2013
    ..Great progress has been made on the mechanisms controlling BMP signaling from the ligands in the extracellular environment, through their receptors and into the nucleus...
  30. Local Calcium Signaling in Pulmonary Arteries
    JAMES SK SHAM; Fiscal Year: 2012
    ..Since RyR subtypes are dissimilar in their Ca2+ sensitivity for activation and their affinity to various ligands, their heterogeneous distribution raises the intriguing possibility that they may regulate independently ..
  31. Dual-Receptor Targeted Nanoparticles for Photodynamic Therapy of Brain Cancer
    Ann Marie Broome; Fiscal Year: 2013
    ..cross-disciplinary approach to synthesize PEG-coated gold nanoparticles conjugated to Pc 4 and tethered peptide ligands for targeting epidermal growth factor (EGF) and transferrin (Tf) cell surface receptors, which are overexpressed ..
  32. Neuroprotection by IFN-beta in AIDS
    Marcus Kaul; Fiscal Year: 2013
    ..IFN? induces in M? and microglia natural ligands of the HIV coreceptor CCR5, such as MIP-1??? and RANTES, which inhibit HIV-1 infection...
  33. Pax8-PPARgamma regulation of transcription and metabolism in thyroid cancer
    RONALD JAY KOENIG; Fiscal Year: 2013
    ..In Specific Aim 3, the effects of PPARg ligands (thiazolidinediones) on xenograft tumor and metastasis formation will be evaluated in NOD-SCID mice...
  34. Aryl Hydrocarbon Receptor Modulators for the Treatment of Hepatocellular Carcinom
    Siva Kumar Kolluri; Fiscal Year: 2012
    ..the potential for treatment of cancer We will use in silico structure-based VLS for identifying novel alternative ligands of the AhR...
  35. Transcriptional Regulation of Natriuetic Sensitivity in Diabetes Mellitus
    PATIENCE O OBIH; Fiscal Year: 2012
    ..The thiazolidinediones (TZDs) have been introduced for the treatment of type 2 diabetes. These agents are ligands for peroxisome proliferator activated gamma receptors (PPAR3) and are used in type 2 diabetes since they work by ..
  36. INTERACTION OF THE ESTROGEN RECEPTOR WITH DNA
    ANN NARDULLI; Fiscal Year: 2013
    ..The insights gained will help delineate how estrogens and other hormonal ligands regulate gene expression in the brain, enhance our understanding of the cellular responsiveness of the brain to ..
  37. Regulation of PTHrP in Squamous Cell Carcinoma by the EGF Receptor
    GWENDOLEN LORCH; Fiscal Year: 2010
    ..The overall hypothesis to be tested is that EGF ligands act in an autocrine manner with the EGFR to regulate PTHrP expression in lung SCC and induce the development of ..
  38. Mechanisms of innate immune response modulation by mechanical ventilation
    William A Altemeier; Fiscal Year: 2012
    ..is (a) specific for individual TLR- signaling pathways and/or (b) dependent on generation of endogenous TLR ligands. This aim is accomplished through the combination of highly specific toll-like receptor agonists and genetically ..
  39. Androgen Receptor Pathway and Risk of Hepatic Fibrosis in Hepatitis C
    DONNA LORRAINE WHITE; Fiscal Year: 2013
    ..Experimental data suggests the AR and also its androgen ligands including the primary male sex hormone testosterone may play a role in increasing risk of liver cancer due to ..
  40. EXPRESSION PROFILES FOR RET-POSITIVE DRG NEURONS
    Sanjay Jain; Fiscal Year: 2013
    ..We study a subtype of nociceptor that depends on glial cell line-derive neurotrophic factor (GDNF) family ligands (GFLs) for postnatal survival...
  41. REGULATION OF GENE EXPRESSION BY DNA BINDING LIGANDS
    Peter B Dervan; Fiscal Year: 2013
    ..Thus the proposed research is relevant to NIH's mission that pertains to developing fundamental knowledge that will create new therapeutic targets for alleviating disease. ..
  42. Structure and Function of the Hepatitis C Virus Genome
    Peter Sarnow; Fiscal Year: 2013
    ..Secondly, we will study the interaction of RNA helicase RIG-I with viral and host RNA ligands. Specifically, a cell-based crosslinking-immunoprecipitation (CLIP) assay will be employed to identify HCV and ..
  43. Chemokine Decoy Receptor for Therapy of Autoimmune Arthritis
    Kanneganti Murthy; Fiscal Year: 2012
    ..Ig-Fc and the second ecto domain of the CCR5 receptor, hR-421 binds and neutralizes al 3 CCR5-binding chemokine ligands (MIP-?, MIP-?, RANTES) and prevents their binding and activation of the CCR1, CCR3, and CCR5 membrane receptors...
  44. KINETICS OF DRUG MACROMOLECULE COMPLEX FORMATION
    PALMER WILLIAM TAYLOR; Fiscal Year: 2013
    ..In turn, they have spun off separate drug development endeavors directed novel nicotinic receptor ligands for depression, schizophrenia, pain alleviation and nicotine addiction and AChE inhibitor antidotes...
  45. Role of formyl peptide receptor variants in mucosal innate immune defense
    HEINI MARITA MIETTINEN; Fiscal Year: 2010
    ..of certain bacterial components: For example, mutations in NOD2 and TLR-4 that affect binding of their ligands (bacterial muramyl dipeptide and LPS) have been shown to be associated with some Crohn's disease cases...
  46. Design and Synthesis of Anxioselective Anxiolytics
    James M Cook; Fiscal Year: 2010
    ..serve as the lead compounds in this study directed toward the synthesis of alpha2 and alpha3 subtype selective ligands. Moreover, these agents should be long-lived, metabolically stable, water soluble, orally active anxiolytic ..
  47. MOLECULAR BIOLOGY OF HEMORRHAGIC SHOCK
    Timothy R Billiar; Fiscal Year: 2013
    ..and TLR4 are markedly unregulated and can induce an exaggerated inflammatory response if triggered by microbial ligands. Data from our PI's indicate tissue-specific expression and function patterns for TLR2 and TLR9...
  48. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
    ..protein (LRP-1 or LRP), a large endocytic receptor that plays an important role in the catabolism of several ligands including apoE-enriched lipoproteins, plasminogen activators, and serpin-enzyme complexes...
  49. Pharmacological strategies to improve breathing after cervical spinal cord injury
    FRANCIS GOLDER; Fiscal Year: 2009
    ..mimics neurotrophins by transactivating their tropomyosin-related kinase (Trk) receptors in the absence of Trk ligands. We recently demonstrated that cervical spinal administration of CGS 21680 strengthens spinal synaptic ..
  50. MIF AND THE HOST RESPONSE TO INFECTION
    RICHARD J BUCALA; Fiscal Year: 2013
    ..will characterize the MIF-dependent responses of human monocytes and alveolar epithelial cells stimulated by TLR ligands that are representative of diverse microbial pathogens...
  51. Preclinical drug trial in mouse models of inflammation
    Kanneboyina Nagaraju; Fiscal Year: 2013
    ..Thus, ligands that preferentially induce the transrepression and not transactivation function of the GR are ideal for treating ..
  52. Optimization of EphA4 antagonists for CNS disorders
    ELENA B contact PASQUALE; Fiscal Year: 2010
    ..In the embryonic nervous system, EphA4 interaction with its membrane-associated ligands - the ephrins - are critical for axon guidance as well as for the formation of tissue boundaries...
  53. PROBES FOR CYTOMETRY
    Zbigniew Darzynkiewicz; Fiscal Year: 2013
    ..The first approach analyzes changes in the maximal pixel intensity of fluorescence of DNA-bound fluorescent ligands, a reporter of chromatin relaxation, the initial event in a cell's DNA damage response (DDR)...
  54. Control of Drug Delivery to the CNS: Modulating P-glycoprotein Activity
    William A Banks; Fiscal Year: 2013
    ..P-gp is a brain-to-blood (efflux) pump located in the luminal side of the BBB that prevents its ligands from entering the CNS. P-gp has an affinity for an incredibly large number of clinically used drugs...
  55. Chronic Granulomatous Lung Inflammation Elicited by Carbon Nanotubes
    Mary Jane Thomassen; Fiscal Year: 2013
    ..In contrast, proinflammatory CCR5 ligands are not found in healthy lung but are elevated in sarcoidosis...
  56. The lymph node microenvionment in tumor metastasis
    Judith A Varner; Fiscal Year: 2012
    ..of tumor cells by expressing key tumor cell chemoattractants such as CCL21 as well as tumor cell adhesion ligands/receptors, such as integrin ?4?1, VCAM and E-Selectin;and that inflammatory mediators and bone marrow derived ..
  57. CCR3: a molecular marker for neovascular AMD
    Jayakrishna Ambati; Fiscal Year: 2010
    ..Targeting CCR3 or its eotaxin ligands inhibited angiogenesis in vitro and in vivo, and was both superior to and safer than VEGF-A blockade...
  58. Nanomedicine and NeuroAIDS
    Howard E Gendelman; Fiscal Year: 2013
    ..This will readily permit evaluation of broad numbers of coating ligands. Fourth, we will evaluate the functional consequences to the cell as it is linked to intracellular particle ..
  59. Regulation of Signaling Receptor Activity by LRP-1
    Steven L Gonias; Fiscal Year: 2013
    ..protein-1 (LRP-1) is a transmembrane receptor that mediates the endocytosis of over forty distinct ligands and other plasma membrane proteins. LRP-1 also regulates cell-signaling by two distinct mechanisms...
  60. Stem Cell Based Therapy For Radiation Induced Gastrointestinal Syndrome
    Chandan Guha; Fiscal Year: 2010
    ..mucosal disruption, resident macrophages in the intestinal submucosal layers are activated by pathogen-derived ligands for Toll-like receptors (TLR) and upon activation, macrophages act as "mobile cellular transceivers" that ..
  61. Carbohydrate-based Antiinfective Agents
    Chi Huey Wong; Fiscal Year: 2013
    ..anti-infective is that they are less prone to the evolution of microbial resistance, because, carbohydrate ligands themselves are invariant, and carbohydrate recognition is essential to pathogenic function...
  62. Repair of Airway Epithelium Following Chlorine Lung Injury
    Gary W Hoyle; Fiscal Year: 2011
    ..NGFR binds multiple neurotrophin ligands, including nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin 3...
  63. The RAGE of COPD
    John R Hoidal; Fiscal Year: 2013
    ..We propose a new paradigm for a central role of the receptor for advanced glycation end products (RAGE) and its ligands in the emphysema pathogenesis...
  64. Regulation of Fibronectin Matrix Assembly by uPAR
    PAULA J MC KEOWN-LONGO; Fiscal Year: 2012
    ..EGFR dimerization, ubiquitination, sequestration and degradation in response to uPAR or EGFR ligands will be analyzed by Western blot, FLOW cytometry and confocal microscopy...
  65. Lipid glyceryl ester homeostasis in macrophages and perturbation by environmental
    Matthew K Ross; Fiscal Year: 2012
    ..The ECS is composed of several components, including CB receptors, ligands (2-arachidonoylglycerol, 2AG;anandamide, AEA), endocannabinoid biosynthetic enzymes, transporters, and hydrolytic ..
  66. Selection and Characterization of PSMA Ligands from Phage-Displayed Libraries
    Gary Fujii; Fiscal Year: 2006
    ..focus on prostate cancer as a model disease to demonstrate technology for the rapid selection of high affinity ligands to a specific tumor marker, in this case, PSMA. Dr...
  67. Hunting for Endogenous Ligands for Invariant Natural Killer T Cells
    Peng George Wang; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): This research program targets at the search for the true endogenous ligands for the iNKT cells development...
  68. CELL SURFACE LECTINS AND INTERCELLULAR ADHESION
    Steven Rosen; Fiscal Year: 2009
    ..The rolling step is mediated by L-selectin, which recognizes a set of carbohydrate-based ligands on HEVs. The predominant ligands are sialomucins modified by sulfated sLex determinants and are known as PNAd...
  69. ENTEROBACTIN DERIVATIVES: BUILDING A BETTER FERRIC TRAP
    Carlos Gutierrez; Fiscal Year: 1991
    ..lactone nucleus to which are appended three exocyclic 2,3-dihydroxybenzamide units which serve as the binding ligands for Fe(III). However, the compound is unsuitable as a therapeutic agent as it promotes the growth of E. Coli...
  70. DNA-modulated release of drug from melanoma targeting NP
    Kit Lam; Fiscal Year: 2009
    ..of nano-therapeutic or nano-imaging agents is the lack of high affinity and high specificity targeting ligands that can deliver these nanomedicines to the tumor or organ target site with high efficiency in vivo...
  71. PPAR- GAMMA LIGANDS IN ULCERATIVE COLITIS
    James Lewis; Fiscal Year: 2001
    ..superfamily of transcription factors whose activities are regulated by high affinity binding of small lipophilic ligands such as steroid hormones...
  72. Bivalent ligands as molecular probes for CB1/OX1 receptor heterodimers
    Yanan Zhang; Fiscal Year: 2010
    ..Bivalent ligands, provided they have suitable monomeric receptor affinities and function, are expected to selectively bind with ..
  73. Tolerance to TLR Ligands in the Intestinal Epithelium
    Anatoly V Grishin; Fiscal Year: 2010
    ..receptors (TLR), and produce inflammatory factors in response to stimulation with luminal bacteria or their TLR ligands. These responses are critical for gut maintenance because they promote mutualistic relationship between ..
  74. Development of Opioid Receptor Models for Rational Design of Bifunctional Ligands
    JUDITH HOBRATH; Fiscal Year: 2009
    ..Recent research using opioid receptor subtype selective antagonist and agonist ligands as well as gene knock out studies have provided convincing evidence that the blockade of opioid delta receptors ..
  75. Functional Selection of Novel Ligands from the Neuroendocrine Secretome
    David Larocca; Fiscal Year: 2010
    ..We will use a novel phage particle display strategy designed to identify active ligands from within larger protein precursors to identify novel ligands and their target cells...
  76. NOVEL SIGMA RECEPTOR LIGANDS IN NEURODEGENERATION
    Raymond Booth; Fiscal Year: 2000
    ..We have designed a series of phenylamino- substituted tetrahydro-naphthalene (phenylaminotetralin, PAT) ligands and radioligands that have very high affinity (e.g...