structure activity relationship

Summary

Summary: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects.

Top Publications

  1. ncbi Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18)
    J O Lee
    Laboratory of X ray Crystallography, Dana Farber Cancer Institute, Harvard Medical School Boston, Massachusetts 02115
    Cell 80:631-8. 1995
  2. ncbi Structure of a bacterial multidrug ABC transporter
    Roger J P Dawson
    Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
    Nature 443:180-5. 2006
  3. ncbi The principle of gating charge movement in a voltage-dependent K+ channel
    Youxing Jiang
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 423:42-8. 2003
  4. 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
  5. ncbi Ion conduction pore is conserved among potassium channels
    Z Lu
    Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA
    Nature 413:809-13. 2001
  6. 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
  7. ncbi Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm
    P E Wright
    Department of Molecular Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Mol Biol 293:321-31. 1999
  8. ncbi Protein tyrosine phosphatases: from genes, to function, to disease
    Nicholas K Tonks
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Rev Mol Cell Biol 7:833-46. 2006
  9. ncbi Intrinsically unstructured proteins
    Peter Tompa
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, 1518, PO Box 7, Budapest, Hungary
    Trends Biochem Sci 27:527-33. 2002
  10. 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

Detail Information

Publications245 found, 100 shown here

  1. ncbi Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18)
    J O Lee
    Laboratory of X ray Crystallography, Dana Farber Cancer Institute, Harvard Medical School Boston, Massachusetts 02115
    Cell 80:631-8. 1995
    ..Our crystal structure will allow reliable models to be built for other members of the A domain superfamily and should facilitate development of novel adhesion modulatory drugs...
  2. ncbi Structure of a bacterial multidrug ABC transporter
    Roger J P Dawson
    Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
    Nature 443:180-5. 2006
    ....
  3. ncbi The principle of gating charge movement in a voltage-dependent K+ channel
    Youxing Jiang
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 423:42-8. 2003
    ..Our findings lead us to conclude that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore...
  4. 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...
  5. ncbi Ion conduction pore is conserved among potassium channels
    Z Lu
    Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA
    Nature 413:809-13. 2001
    ..The resulting chimaeras retain the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among K+ channels...
  6. 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...
  7. ncbi Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm
    P E Wright
    Department of Molecular Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Mol Biol 293:321-31. 1999
    ....
  8. ncbi Protein tyrosine phosphatases: from genes, to function, to disease
    Nicholas K Tonks
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Rev Mol Cell Biol 7:833-46. 2006
    ..In this review, I describe recent breakthroughs in our understanding of the role of the PTPs in the regulation of signal transduction and the aetiology of human disease...
  9. ncbi Intrinsically unstructured proteins
    Peter Tompa
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, 1518, PO Box 7, Budapest, Hungary
    Trends Biochem Sci 27:527-33. 2002
    ..In this review, recent findings are surveyed to illustrate that this novel but rapidly advancing field has reached a point where these proteins can be comprehensively classified on the basis of structure and function...
  10. 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...
  11. ncbi IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content
    Zsuzsanna Dosztanyi
    Institute of Enzymology, BRC, Hungarian Academy of Sciences, PO Box 7, H 1518 Budapest, Hungary
    Bioinformatics 21:3433-4. 2005
    ..Optional to the prediction are built-in parameter sets optimized for predicting short or long disordered regions and structured domains...
  12. pmc Differential effects of beta 1 and beta 2 subunits on BK channel activity
    Patricio Orio
    Centro de Estudios Cientificos, Valdivia, Chile
    J Gen Physiol 125:395-411. 2005
    ..All allosteric coupling factors need to be increased in order to explain the observed effects when the alpha subunit is coexpressed with the beta2IR subunit...
  13. ncbi Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors
    Craig W Lindsley
    Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck Research Laboratories, Merck and Co, PO Box 4, West Point, PA 19486, USA
    Bioorg Med Chem Lett 15:761-4. 2005
    ..An iterative analog library synthesis approach quickly provided a highly selective Akt1/Akt2 inhibitor that induces apoptosis in tumor cells and inhibits Akt phosphorylation in vivo...
  14. ncbi Intrinsic disorder and protein function
    A Keith Dunker
    School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA
    Biochemistry 41:6573-82. 2002
  15. ncbi The polynucleotide ligase and RNA capping enzyme superfamily of covalent nucleotidyltransferases
    Stewart Shuman
    Molecular Biology and Structural Biology Programs, Sloan Kettering Institute for Cancer Research, New York, New York 10021, USA
    Curr Opin Struct Biol 14:757-64. 2004
    ..The first crystal structure of an RNA ligase suggests that contemporary DNA ligases, RNA ligases and RNA capping enzymes evolved by fusion of ancillary effector domains to an ancestral catalytic module involved in RNA repair...
  16. ncbi Regulation of protein kinases; controlling activity through activation segment conformation
    Brad Nolen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92116, USA
    Mol Cell 15:661-75. 2004
    ..Here we examine these structures using a structural bioinformatics approach to understand how the conformation of the activation segment controls kinase activity...
  17. ncbi From protein structure to biochemical function?
    Roman A Laskowski
    European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
    J Struct Funct Genomics 4:167-77. 2003
    ..Here we present three examples, using structures solved by the Midwest Center for Structural Genomics consortium, illustrating the strengths and weaknesses of current approaches...
  18. pmc A network representation of protein structures: implications for protein stability
    K V Brinda
    Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India
    Biophys J 89:4159-70. 2005
    ..Based on these results, we also predict a few residues in the thermophilic and mesophilic proteins that can be mutated to alter their thermal stability...
  19. ncbi Induction of cell cycle arrest in lymphocytes by Actinobacillus actinomycetemcomitans cytolethal distending toxin requires three subunits for maximum activity
    Bruce J Shenker
    Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA
    J Immunol 174:2228-34. 2005
    ..The implications of our results with respect to the function and structure of the Cdt holotoxin are discussed...
  20. ncbi SNPs, protein structure, and disease
    Z Wang
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA
    Hum Mutat 17:263-70. 2001
    ..In sharp contrast, over 70% of the population set are found to be neutral. The remaining 30% are potentially involved in polygenic disease...
  21. ncbi Voltage-dependent gating of hyperpolarization-activated, cyclic nucleotide-gated pacemaker channels: molecular coupling between the S4-S5 and C-linkers
    Niels Decher
    Department of Physiology and Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112 5000, USA
    J Biol Chem 279:13859-65. 2004
    ....
  22. ncbi Molecular basis of proton blockage in aquaporins
    Nilmadhab Chakrabarti
    Structural Biology and Biochemistry, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    Structure 12:65-74. 2004
    ..Inversely, translocation of an excess proton in either direction is opposed by a free-energy barrier centered at the NPA region. Both hop and turn steps of proton translocation are opposed by the electrostatic field of the channel...
  23. ncbi Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms
    R Manjunatha Kini
    Protein Science Laboratory, Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
    Toxicon 45:1147-61. 2005
    ..Thus, these studies strongly support the target model which suggests that protein-protein interaction rather than protein-phospholipid interaction determines the pharmacological specificity of PLA(2) enzymes...
  24. ncbi Analysis of catalytic residues in enzyme active sites
    Gail J Bartlett
    Department of Biochemistry and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK
    J Mol Biol 324:105-21. 2002
    ..It is hoped that this information will provide a better understanding of the molecular mechanisms involved in catalysis and a heuristic basis for predicting catalytic residues in enzymes of unknown function...
  25. ncbi FACS-optimized mutants of the green fluorescent protein (GFP)
    B P Cormack
    Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305 5402, USA
    Gene 173:33-8. 1996
    ..coli, the folding of the mutant proteins is more efficient than folding of wt GFP. These two properties contribute to a greatly increased (100-fold) fluorescence intensity, making the mutants useful for a number of applications...
  26. ncbi Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast
    Gwan Sub Sim
    R and D Center, Hanbul Cosmetics Co, Chungbuk 369 830, Korea
    Arch Pharm Res 30:290-8. 2007
    ....
  27. ncbi Analysis of drug-induced effect patterns to link structure and side effects of medicines
    Anton F Fliri
    Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA
    Nat Chem Biol 1:389-97. 2005
    ..The identification of this alignment provides a mechanism for forecasting clinical effect profiles of medicines...
  28. 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...
  29. ncbi Docking and scoring in virtual screening for drug discovery: methods and applications
    Douglas B Kitchen
    Department of Computer Aided Drug Discovery, Albany Molecular Research, Inc, 21 Corporate Circle, Albany, New York 12212 5098, USA
    Nat Rev Drug Discov 3:935-49. 2004
    ..Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches...
  30. ncbi Closing the folding chamber of the eukaryotic chaperonin requires the transition state of ATP hydrolysis
    Anne S Meyer
    Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA
    Cell 113:369-81. 2003
    ..Understanding the distinct mechanisms governing eukaryotic and bacterial chaperonin function may reveal how TRiC has evolved to fold specific eukaryotic proteins...
  31. ncbi Structural mechanism for STI-571 inhibition of abelson tyrosine kinase
    T Schindler
    Laboratories of Molecular Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 289:1938-42. 2000
    ..These results suggest that compounds that exploit the distinctive inactivation mechanisms of individual protein kinases can achieve both high affinity and high specificity...
  32. ncbi The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I
    Sheng Cui
    Gene Center, Department of Chemistry and Biochemistry, Ludwig Maximilians University of Munich, Feodor Lynen Strasse 25, 81377 Munich, Germany
    Mol Cell 29:169-79. 2008
    ..Structure-guided mutagenesis identifies a positively charged groove as likely 5'-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity...
  33. ncbi Structural basis of constitutive activity and a unique nucleotide binding mode of human Pim-1 kinase
    Kevin C Qian
    Departments of Medicinal Chemistry and Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc, Research and Development, 175 Briar Ridge Rd, Ridgefield, CT 06877, USA
    J Biol Chem 280:6130-7. 2005
    ..Analysis of the reported Pim-1 kinase-domain structures leads to a hypothesis as to how Pim kinase activity might be regulated in vivo...
  34. pmc The CATH Database provides insights into protein structure/function relationships
    C A Orengo
    Department of Biochemistry and Molecular Biology, Darwin Building, Univeristy College London, Gower Street, London WC1E 6BT, UK
    Nucleic Acids Res 27:275-9. 1999
    ..Our analysis supports the view that determining structures, for example as part of a 'structural genomics' initiative, will make a major contribution to interpreting genome data...
  35. ncbi Managing protein flexibility in docking and its applications
    Chandrika B-Rao
    Discovery Informatics, Piramal Life Sciences Limited, 1 Nirlon Complex, Off Western Express Highway, Goregaon E, Mumbai 400063, India
    Drug Discov Today 14:394-400. 2009
    ..We conclude, from a comparison of the different approaches, that a combination of methods is likely to provide the most reliable solution to the problem of finding the right protein conformation for a given ligand...
  36. ncbi 'Metabolite-likeness' as a criterion in the design and selection of pharmaceutical drug libraries
    Paul D Dobson
    School of Chemistry and The Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess St, Manchester M1 7DN, UK
    Drug Discov Today 14:31-40. 2009
    ....
  37. pmc Analysis of full and partial agonists binding to beta2-adrenergic receptor suggests a role of transmembrane helix V in agonist-specific conformational changes
    VSEVOLOD KATRITCH
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Mol Recognit 22:307-18. 2009
    ....
  38. pmc AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity
    Sebastien Dutertre
    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
    EMBO J 26:3858-67. 2007
    ..Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases...
  39. ncbi Biochemical, cellular, and pharmacological aspects of the multidrug transporter
    S V Ambudkar
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Pharmacol Toxicol 39:361-98. 1999
    ..This review summarizes current research on the structure-function analysis of P-glycoprotein, its mechanism of action, and facts and speculations about its normal physiological role...
  40. pmc Detection of novel members, structure-function analysis and evolutionary classification of the 2H phosphoesterase superfamily
    Raja Mazumder
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
    Nucleic Acids Res 30:5229-43. 2002
    ..Initially, this domain appears to have been involved in RNA processing and it appears to have been recruited to perform various other functions in later stages of evolution...
  41. pmc Structure-based discovery of novel chemotypes for adenosine A(2A) receptor antagonists
    VSEVOLOD KATRITCH
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 53:1799-809. 2010
    ..High success rate, novelty, and diversity of the chemical scaffolds and strong ligand efficiency of the A(2A)AR antagonists identified in this study suggest practical applicability of receptor-based VLS in GPCR drug discovery...
  42. pmc Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring
    J B Gorlin
    Department of Medicine, Massachusetts General Hospital, Charlestown
    J Cell Biol 111:1089-105. 1990
    ..The large size of the leaves, their interruption by two hinges and flexible actin-binding site, facilitate cross-linking of widely dispersed actin filaments...
  43. ncbi The structure and function of proline recognition domains
    Ali Zarrinpar
    Program in Biological Sciences, University of California San Francisco, 600 16th Street, San Francisco, CA 94143 2240, USA
    Sci STKE 2003:RE8. 2003
    ..These domains use strikingly similar molecular mechanisms of proline recognition. We discuss some of the potential biological advantages conferred by proline recognition, which may explain its widespread use in signaling...
  44. ncbi BaCelLo: a balanced subcellular localization predictor
    Andrea Pierleoni
    Biocomputing Group, Dept of Biology University of Bologna, Via Irnerio 42, 40126 Bologna, Italy
    Bioinformatics 22:e408-16. 2006
    ..Computational procedures are then needed for annotating the subcellular location of proteins in large scale genomic projects...
  45. ncbi The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel
    D L Minor
    Howard Hughes Medical Institute and Department of Physiology, University of California, San Francisco 94143, USA
    Cell 102:657-70. 2000
    ..Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening...
  46. ncbi Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition
    Nebojsa Mirkovic
    Laboratory of Molecular Biophysics, Pels Family Center for Biochemistry and Structural Biology, Rockefeller University, New York, New York, USA
    Cancer Res 64:3790-7. 2004
    ..Such a structure-based approach may be helpful in an integrated effort to identify mutations that predispose individuals to cancer...
  47. pmc Measurements of the BKCa channel's high-affinity Ca2+ binding constants: effects of membrane voltage
    Tara Beth Sweet
    Molecular Cardiology Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA
    J Gen Physiol 132:491-505. 2008
    ....
  48. 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...
  49. ncbi Heterotachy, an important process of protein evolution
    P Lopez
    Phylogénie, Bioinformatique et Génome, CNRS, Universite Pierre et Marie Curie, 9, quai St Bernard, 75005 Paris, France
    Mol Biol Evol 19:1-7. 2002
    ..The observations made here open several new avenues of research, such as the understanding of the evolution of functional constraints or the improvement of phylogenetic reconstruction methods...
  50. ncbi Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer analogs
    Kristina M Smith
    Department of Biological Sciences, University at Buffalo, State University of New York, 14260, USA
    Chem Biol 10:81-9. 2003
    ..We performed a series of assays to show that inhibition of quorum sensing by these antagonists significantly reduced the production of virulence factors and biofilm formation...
  51. ncbi Multiple molecular mechanisms for multidrug resistance transporters
    Christopher F Higgins
    MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
    Nature 446:749-57. 2007
    ..Answers are emerging to questions such as how multispecificity for different drugs is achieved, why multidrug resistance arises so readily, and what chance there is of devising a clinical solution...
  52. ncbi Structural basis for the selective activation of Rho GTPases by Dbl exchange factors
    Jason T Snyder
    Department of Biochemistry and Biophysics, Program in Molecular and Cellular Biophysics, Chapel Hill, North Carolina 27599, USA
    Nat Struct Biol 9:468-75. 2002
    ....
  53. ncbi Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation
    Marlies Van de Wouwer
    The Center for Transgene Technology and Gene Therapy, University of Leuven and the Flanders Interuniversity Institute for Biotechnology VIB, Belgium
    Arterioscler Thromb Vasc Biol 24:1374-83. 2004
    ..Overall, the described advances underscore the usefulness of elucidating the relevant molecular pathways that link both systems for the development of novel therapeutic and diagnostic targets for a wide range of inflammatory diseases...
  54. ncbi Novel 4-anilinoquinazolines with C-7 basic side chains: design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors
    Laurent F Hennequin
    AstraZeneca, Centre de Recherches, Z I la Pompelle, B P 1050, Chemin de Vrilly, 51689 Reims, Cedex 2, France
    J Med Chem 45:1300-12. 2002
    ..001, Mann Whitney rank sum test), and substantial inhibition (36%, P < 0.02) was evident with 12.5 mg/kg/day...
  55. pmc SCOR: a Structural Classification of RNA database
    Peter S Klosterman
    Physical Biosciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Nucleic Acids Res 30:392-4. 2002
    ..A classification of the well-characterized tertiary interactions found in the larger RNA structures is also included along with examples. The SCOR database is accessible at http://scor.lbl.gov...
  56. ncbi NMR analysis of structure and dynamics of the cytosolic tails of integrin alpha IIb beta 3 in aqueous solution
    T S Ulmer
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
    Biochemistry 40:7498-508. 2001
    ....
  57. ncbi Presynaptic Ca2+ channels--integration centers for neuronal signaling pathways
    Rhian M Evans
    Hotchkiss Brain Institute, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    Trends Neurosci 29:617-24. 2006
    ..Here, we provide a broad overview of molecular and cellular mechanisms that regulate Ca2+ channels, and how these cellular signaling pathways are integrated at the level of the channel protein...
  58. ncbi Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity
    Stanley S Ng
    Structural Genomics Consortium, Botnar Research Center, University of Oxford, Oxford OX3 7LD, UK
    Nature 448:87-91. 2007
    ....
  59. ncbi Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core
    N Armstrong
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA
    Neuron 28:165-81. 2000
    ..The crystal packing of the ligand binding cores suggests modes for subunit-subunit contact in the intact receptor and mechanisms by which allosteric effectors modulate receptor activity...
  60. pmc Stabilization of the activity of ATP-sensitive potassium channels by ion pairs formed between adjacent Kir6.2 subunits
    Yu Wen Lin
    Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97239, USA
    J Gen Physiol 122:225-37. 2003
    ..The structure lends support to our findings in Kir6.2, and raises the possibility that a homologous ion pair may be involved in the gating of GIRKs...
  61. ncbi Thiolated polymers--thiomers: synthesis and in vitro evaluation of chitosan-2-iminothiolane conjugates
    Andreas Bernkop-Schnürch
    Center of Pharmacy, Institute of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, A 1090 Vienna, Austria
    Int J Pharm 260:229-37. 2003
    ..The modification of chitosan with 2-iminothiolane leads, therefore to thiolated polymers, which represent a promising tool for the development of in situ gelling and/or mucoadhesive drug delivery systems...
  62. pmc Cleavage of the human respiratory syncytial virus fusion protein at two distinct sites is required for activation of membrane fusion
    L Gonzalez-Reyes
    Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
    Proc Natl Acad Sci U S A 98:9859-64. 2001
    ..Both cleavages are required for the F protein to be active in membrane fusion as judged by syncytia formation, and they allow changes in F structure from cone- to lollipop-shaped spikes and the formation of rosettes by anchorless F...
  63. pmc Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins
    Travis P Schrank
    Department of Biochemistry and Molecular Biology, and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA
    Proc Natl Acad Sci U S A 106:16984-9. 2009
    ..These findings open new avenues for rational protein design and fundamentally illuminate the role of local unfolding in function and adaptation...
  64. pmc Positive selection detection in 40,000 human immunodeficiency virus (HIV) type 1 sequences automatically identifies drug resistance and positive fitness mutations in HIV protease and reverse transcriptase
    Lamei Chen
    Molecular Biology Institute, Center for Genomics and Proteomics, Dept of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095 1570, USA
    J Virol 78:3722-32. 2004
    ..bioinformatics.ucla.edu/HIV. Our data indicate that positive selection mapping is an analysis that can yield powerful insights from high-throughput sequencing of rapidly mutating pathogens...
  65. ncbi The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen
    A K Shiau
    Howard Hughes Medical Institute and the Department of Biochemistry and Biophysics, University of California at San Francisco, 94143 0448, USA
    Cell 95:927-37. 1998
    ..These structures reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation...
  66. ncbi SH3-dependent stimulation of Src-family kinase autophosphorylation without tail release from the SH2 domain in vivo
    Edwina C Lerner
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Nat Struct Biol 9:365-9. 2002
    ....
  67. ncbi Intrinsic dynamics of an enzyme underlies catalysis
    Elan Z Eisenmesser
    Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA
    Nature 438:117-21. 2005
    ..We propose that the pre-existence of collective dynamics in enzymes before catalysis is a common feature of biocatalysts and that proteins have evolved under synergistic pressure between structure and dynamics...
  68. pmc A new measure for functional similarity of gene products based on Gene Ontology
    Andreas Schlicker
    Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Stuhlsatzenhausweg 85, 66123 Saarbrucken, Germany
    BMC Bioinformatics 7:302. 2006
    ..These annotations provide a basis for new methods that compare gene products regarding their molecular function and biological role...
  69. ncbi Discovery of 2,3,5-trisubstituted pyridine derivatives as potent Akt1 and Akt2 dual inhibitors
    Zhijian Zhao
    Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck Research Laboratories, Merck and Co, PO Box 4, West Point, PA 19486, USA
    Bioorg Med Chem Lett 15:905-9. 2005
    ..Compounds from this series, which contain a 5-tetrazolyl moiety, exhibit more potent inhibition of Akt2 than Akt1...
  70. ncbi CLANS: a Java application for visualizing protein families based on pairwise similarity
    Tancred Frickey
    Max Planck Institut fuer Entwicklungsbiologie, Spemannstrasse 35, 72076 Tuebingen, Germany
    Bioinformatics 20:3702-4. 2004
    ..AVAILABILITY: CLANS can be downloaded at http://protevo.eb.tuebingen.mpg.de/download...
  71. ncbi Comparative assessment of scoring functions on a diverse test set
    Tiejun Cheng
    State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, P R China
    J Chem Inf Model 49:1079-93. 2009
    ..Our results indicate that no single scoring function consistently outperforms others in all three aspects. Thus, it is important in practice to choose the appropriate scoring functions for different purposes...
  72. pmc Conservation of intrinsic disorder in protein domains and families: I. A database of conserved predicted disordered regions
    Jessica Walton Chen
    Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 46202, USA
    J Proteome Res 5:879-87. 2006
    ..Most regions of conserved predicted disorder detected were short, with less than 10% of those found exceeding 30 residues in length...
  73. ncbi Metallo-beta-lactamase: structure and mechanism
    Z Wang
    The Pennsylvania State University, Department of Chemistry, 152 Davey Laboratory, University Park, PA 16802, USA
    Curr Opin Chem Biol 3:614-22. 1999
    ..These advances shed light on how such a diverse group of enzymes are evolving to inactivate so efficiently a broad spectrum of beta-lactam antibiotics...
  74. ncbi Structure and mechanism of Na,K-ATPase: functional sites and their interactions
    Peter L Jorgensen
    Biomembrane Center, August Krogh Institute, Copenhagen University, Universitetsparken 13, 2100 Copenhagen OE, Denmark
    Annu Rev Physiol 65:817-49. 2003
    ....
  75. ncbi Protein thermostability in Archaea and Eubacteria
    S Trivedi
    Department of Zoology, JN Vyas University, Jodhpur Raj, India
    Genet Mol Res 5:816-27. 2006
    ..Therefore, it appears that no single factor or combination of factors together can be universally attributed to the provision of thermal stability in proteins...
  76. ncbi Viral RNA pseudoknots: versatile motifs in gene expression and replication
    Ian Brierley
    Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK ib
    Nat Rev Microbiol 5:598-610. 2007
    ..The relationship between RNA pseudoknot structure and function is also addressed...
  77. pmc Protein-ligand interaction prediction: an improved chemogenomics approach
    Laurent Jacob
    Mines ParisTech, Centre for Computational Biology, 35 rue Saint Honore, F 77305 Fontainebleau, Institut Curie and INSERM, U900, F 75248, Paris, France
    Bioinformatics 24:2149-56. 2008
    ..However, the accuracy of ligand-based models quickly degrades when the number of known ligands decreases, and in particular the approach is not applicable for orphan receptors with no known ligand...
  78. ncbi Fragment-based lead discovery
    David C Rees
    Astex Technology, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK
    Nat Rev Drug Discov 3:660-72. 2004
  79. ncbi A revised mechanism for the alkaline phosphatase reaction involving three metal ions
    B Stec
    Department of Biochemistry and Cell Biology, W M Keck Center for Computational Biology, Rice University, Houston, TX, 77005, USA
    J Mol Biol 299:1303-11. 2000
    ..A revised mechanism for the catalytic reaction of alkaline phosphatase is proposed on the basis of the two new X-ray crystal structures reported...
  80. ncbi Network pharmacology: the next paradigm in drug discovery
    Andrew L Hopkins
    Division of Biological Chemistry and Drug Discovery, College of Life Science, University of Dundee, Dundee, UK
    Nat Chem Biol 4:682-90. 2008
    ..Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology...
  81. ncbi The human short-chain dehydrogenase/reductase (SDR) superfamily: a bioinformatics summary
    James E Bray
    Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, UK
    Chem Biol Interact 178:99-109. 2009
    ..Currently there are 17 SDR members with an SFS score of zero indicating that almost a quarter of the human SDR superfamily lacks substantial functional annotation...
  82. ncbi Socket: a program for identifying and analysing coiled-coil motifs within protein structures
    J Walshaw
    Centre for Biomolecular Design and Drug Development, School of Biological Sciences, University of Sussex, Falmer, East Sussex, BN1 9QG, UK
    J Mol Biol 307:1427-50. 2001
    ..To illustrate this we give examples of sequence and structural analyses of the structures that are possible using the new data bases, and we present amino acid profiles for the heptad repeats of different motifs...
  83. ncbi RNA structure analysis at single nucleotide resolution by selective 2'-hydroxyl acylation and primer extension (SHAPE)
    Edward J Merino
    Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599 3290, USA
    J Am Chem Soc 127:4223-31. 2005
    ..Modest extensions of the SHAPE approach will allow RNA structure to be monitored comprehensively and at single nucleotide resolution for RNAs of arbitrary sequence and structural complexity and under diverse solution environments...
  84. ncbi Anticancer antifolates: current status and future directions
    John J McGuire
    Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Curr Pharm Des 9:2593-613. 2003
    ..These new analogs are in various stages of preclinical and clinical development...
  85. ncbi Intrinsically unstructured proteins evolve by repeat expansion
    Peter Tompa
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, 1518 Budapest, PO Box 7, Hungary
    Bioessays 25:847-55. 2003
    ....
  86. ncbi Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3
    S Radaev
    Structural Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA
    Immunity 15:1039-49. 2001
    ..Unlike the KIR receptors that recognize a conserved HLA region by a lock-and-key mechanism, NKG2D recognizes diverse ligands by an induced-fit mechanism...
  87. ncbi High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening
    Tonghui Ma
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Biol Chem 277:37235-41. 2002
    ..The new activators identified here may be useful in defining molecular mechanisms of CFTR activation and as lead compounds in CF drug development...
  88. ncbi Mechanism of auxin perception by the TIR1 ubiquitin ligase
    Xu Tan
    Department of Pharmacology, University of Washington, School of Medicine, Box 357280, Seattle, Washington 98195, USA
    Nature 446:640-5. 2007
    ..By filling in a hydrophobic cavity at the protein interface, auxin enhances the TIR1-substrate interactions by acting as a 'molecular glue'. Our results establish the first structural model of a plant hormone receptor...
  89. ncbi Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck
    M Pelosi
    Molecular Immunology Unit, Institut Pasteur, 25 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France
    J Biol Chem 274:14229-37. 1999
    ..Collectively, our findings indicate that Tyr319-mediated binding of the SH2 domain of Lck is crucial for ZAP-70 activation and consequently for the propagation of the signaling cascade leading to T-cell activation...
  90. ncbi The 1.5 A resolution crystal structure of the carbamate kinase-like carbamoyl phosphate synthetase from the hyperthermophilic Archaeon pyrococcus furiosus, bound to ADP, confirms that this thermostable enzyme is a carbamate kinase, and provides insight in
    S Ramon-Maiques
    Consejo Superior de Investigaciones Cientificas IBV CSIC, Instituto de Biomedicina de Valencia, C Jaime Roig 11, Valencia, 46010, Spain
    J Mol Biol 299:463-76. 2000
    ..The structure provides the first information on substrate binding and catalysis in CKs, and suggests that the slow rate at 37 degrees C is possibly a consequence of slow product dissociation...
  91. ncbi The molecular basis of odor coding in the Drosophila antenna
    Elissa A Hallem
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    Cell 117:965-79. 2004
    ..Receptors vary widely in their breadth of tuning, and odorants vary widely in the number of receptors they activate. Together, these properties provide a molecular basis for odor coding by the receptor repertoire of an olfactory organ...
  92. pmc Structure activity relationship of dendrimer microbicides with dual action antiviral activity
    David Tyssen
    Centres for Virology and Immunology, Burnet Institute, Melbourne, Victoria, Australia
    PLoS ONE 5:e12309. 2010
    ....
  93. ncbi 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatin
    Jagabandhu Das
    Bristol Myers Squibb Pharmaceutical Research Institute, Post Office Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 49:6819-32. 2006
    ..3 and 3 mg/kg twice daily. Dasatinib (2) is currently in clinical trials for the treatment of chronic myelogenous leukemia...
  94. ncbi Sequence-selective DNA recognition: natural products and nature's lessons
    Winston C Tse
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Chem Biol 11:1607-17. 2004
    ..These attributes arise in compact structures of complex integrated function...
  95. pmc Quantifying biogenic bias in screening libraries
    Jérôme Hert
    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA
    Nat Chem Biol 5:479-83. 2009
    ..We have developed a method to quantify the bias in screening libraries toward biogenic molecules. With this approach, we consider what is missing from screening libraries and how they can be optimized...
  96. ncbi Macrocyclic inhibitors of the malarial aspartic proteases plasmepsin I, II, and IV
    Karolina Ersmark
    Department of Medicinal Chemistry, Uppsala University, BMC, PO Box 574, SE 751 23 Uppsala, Sweden
    Bioorg Med Chem 14:2197-208. 2006
    ..The binding mode of this new class of compounds was predicted with automated docking and molecular dynamics simulations, with an estimation of the binding affinities through the linear interaction energy (LIE) method...
  97. ncbi Natively unfolded proteins
    Anthony L Fink
    Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA
    Curr Opin Struct Biol 15:35-41. 2005
    ..New algorithms have been developed to identify disordered regions of proteins and have demonstrated their presence in cancer-associated proteins and proteins regulated by phosphorylation...
  98. ncbi Selective structure-based virtual screening for full and partial agonists of the beta2 adrenergic receptor
    Chris de Graaf
    Bioinformatics of the Drug, Institut Gilbert Laustriat, CNRS UMR 7175 LC1, Universite Louis Pasteur Strasbourg, 74 route du Rhin, 67401 Illkirch, France
    J Med Chem 51:4978-85. 2008
    ..The use of a topological scoring function based on molecular interaction fingerprints was shown to be mandatory to properly rank docking poses and achieve acceptable enrichments for partial and full agonists only...
  99. pmc Visual arrestin binding to microtubules involves a distinct conformational change
    Susan M Hanson
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    J Biol Chem 281:9765-72. 2006
    ..Thus, microtubule and rhodopsin binding induce different conformational changes in arrestin, suggesting that arrestin assumes three distinct conformations in the cell, likely with different functional properties...
  100. ncbi The selectivity of visual arrestin for light-activated phosphorhodopsin is controlled by multiple nonredundant mechanisms
    V V Gurevich
    Sun Health Research Institute, Sun City, Arizona 85372, USA
    J Biol Chem 273:15501-6. 1998
    ..The implications of these findings for the mechanism of arrestin-rhodopsin interaction are discussed in light of the recently determined crystal structure of arrestin...
  101. ncbi Screening drug-like compounds by docking to homology models: a systematic study
    Visvaldas Kairys
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, 20850, USA
    J Chem Inf Model 46:365-79. 2006
    ..Treating key side chains as mobile produces a modest improvement in the results. The reasons for these sometimes unexpected results, and their implications for future methodologic development, are discussed...

Research Grants18

  1. DYNORPHIN MODULATES CGRP RELEASE VIA PKC
    Zaijie Jim Wang; Fiscal Year: 2003
    ..Frank Porreca and Josephine Lai. This award is consistent with the long-term career goal of the candidate to become an independent investigator contributing to the basic research of pain and opioid pharmacology. ..
  2. Inhibitors of the ENT4 Adenosine Transporter for Cardioprotection
    John K Buolamwini; Fiscal Year: 2010
    ..We will investigate structure-activity relationships (SARs) and test the cardioprotective properties of the compounds in an isolated rat heart ischemia model. ..
  3. DRUG SELF-ADMINISTRATION BY INHALATION IN THE PRIMATE
    Ronald Wood; Fiscal Year: 1991
    ....
  4. Discovery of Selective MT1 Melatonin Receptor Ligands for Sleep Disorders
    Margarita L Dubocovich; Fiscal Year: 2010
    ..of in silico ligand-based discovery using phamacophores, virtual screening, and quantitative structure activity relationship and comparative molecular field analysis;2) Determine ligand affinity, agonist potency, and receptor ..
  5. Discovery of 4-aminoquinoline therapeutics for visceral leishmaniasis
    Peter C Melby; Fiscal Year: 2010
    ..This proposal is focused on the discovery of new compounds that will feed into the pipeline bringing new therapeutics to patients with VL. ..
  6. NAAG Peptidase Inhibitors for the Treatment of Traumatic Brain Injury
    Jia Zhou; Fiscal Year: 2009
    ..including ZJ 43, ZJ 11 and ZJ 17 as NAAG peptidase inhibitors with nM potency after extensive structure activity relationship studies...
  7. Development and Applications of Novel SERT PET Ligands
    Mark Goodman; Fiscal Year: 2004
    ..Two goals of this proposal are: 1) conduct a structure activity relationship study (SAR) to identify a sutiable fluorine-18 and bromine-76 radiotracer for in vivo imaging of the ..
  8. Development and Applications of Novel SERT PET Ligands
    Mark Goodman; Fiscal Year: 2006
    ..Two goals of this proposal are: 1) conduct a structure activity relationship study (SAR) to identify a sutiable fluorine-18 and bromine-76 radiotracer for in vivo imaging of the ..
  9. DEVELOPMENT OF VESICULAR ACETYLCHOLINE TRANSPORTER IMAGING AGENTS FOR PET
    Zhude Tu; Fiscal Year: 2010
    ....
  10. Novel Puerarin Analogs with Anti-Diabetic Activity
    NICHOLAS CAIRNS; Fiscal Year: 2007
    ..It is anticipated that these studies will lead to the development of a new class of novel antidiabetic and antiobesity agents based on the puerarin structure. [unreadable] [unreadable] [unreadable]..
  11. DESIGN, SYNTHESIS AND STUDY OF IMPD INHIBITORS
    Wayne Anderson; Fiscal Year: 1993
    ..Potential drug candidates which evolve from the proposed studies will be evaluated for water solubility, chemical stability and other properties that must be assessed in new drug development studies. ..
  12. Compounds Targeting Nematode Secretion as Novel Anti-filarial Drugs
    Bethany Westlund; Fiscal Year: 2006
    ..The overall goal of this project is to discover a new medicine that can effectively treat this unmet need in global health. [unreadable] [unreadable] [unreadable]..
  13. Structure-Activity Relationship in Host Defense Peptides
    GREGORY ALEXANDER CAPUTO; Fiscal Year: 2010
    ....
  14. NON-NITROGEN AND NITROGEN CONTAINING DOPAMINE DRUGS
    Duane Miller; Fiscal Year: 1992
    Based upon the results of our previous structure activity relationship studies, we have developed a hypothesis to explain the interaction of DAergic agonist and antagonist drugs with DAergic receptors...
  15. Canthinones as Human Isozyme Selective PDE4 Inhibitors
    KEVIN CZERWINSKI; Fiscal Year: 2002
    ..for optimum inhibitory activity against human isoforms and the development of a quantitative structure activity relationship to guide the development of new molecular targets has not been explored...
  16. Small molecule modulators for mitochondrial protein import
    Carla Koehler; Fiscal Year: 2009
    ..molecules that target the TIM22 import pathway and alter its function and then develop analogs for structure activity relationship (SAR) studies to identify specific chemical compounds that modulate this pathway and (2) utilize ..
  17. CHALCONE ISOMERASE--MECHANISM OF CATALYSIS
    RODNEY BEDNAR; Fiscal Year: 1990
    ..The research outlined in this proposal will undoubtedly contribute much to our knowledge of the chemistry and reactivity of this class of compounds, as well as the mechanism of action of chalcone isomerase...
  18. Hypocretin agonists as treatments for narcolepsy and wakefulness promotion
    THOMAS KILDUFF; Fiscal Year: 2009
    ....