amino acid substitution

Summary

Summary: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.

Top Publications

  1. ncbi Prediction of deleterious human alleles
    S Sunyaev
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
    Hum Mol Genet 10:591-7. 2001
  2. pmc SIFT: Predicting amino acid changes that affect protein function
    Pauline C Ng
    Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N A1 162, Seattle, WA 98109, USA
    Nucleic Acids Res 31:3812-4. 2003
  3. pmc Predicting deleterious amino acid substitutions
    P C Ng
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genome Res 11:863-74. 2001
  4. pmc Codon-substitution models for heterogeneous selection pressure at amino acid sites
    Z Yang
    Department of Biology, University College London, London NW1 2HE, United Kingdom
    Genetics 155:431-49. 2000
  5. ncbi TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis
    Jemeen Sreedharan
    Department of Clinical Neuroscience, King s College London, Medical Research Council MRC Centre for Neurodegeneration Research, and Institute of Psychiatry, London, SE5 8AF, UK
    Science 319:1668-72. 2008
  6. ncbi A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process
    Nicolas Lartillot
    Canadian Institute for Advanced Research, Departement de Biochimie, Universite de Montreal, Montreal, Quebec Canada
    Mol Biol Evol 21:1095-109. 2004
  7. pmc SNAP: predict effect of non-synonymous polymorphisms on function
    Yana Bromberg
    Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th St, New York, NY 10032, USA
    Nucleic Acids Res 35:3823-35. 2007
  8. ncbi The evolutionary fate and consequences of duplicate genes
    M Lynch
    Department of Biology, University of Oregon, Eugene, OR 97403, USA
    Science 290:1151-5. 2000
  9. pmc Automated inference of molecular mechanisms of disease from amino acid substitutions
    Biao Li
    School of Informatics and Computing, Indiana University, Bloomington, IN 47408, USA
    Bioinformatics 25:2744-50. 2009
  10. pmc Assessing the evolutionary impact of amino acid mutations in the human genome
    Adam R Boyko
    Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA
    PLoS Genet 4:e1000083. 2008

Detail Information

Publications354 found, 100 shown here

  1. ncbi Prediction of deleterious human alleles
    S Sunyaev
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
    Hum Mol Genet 10:591-7. 2001
    ..The average human genotype carries approximately 10(3) damaging non-synonymous SNPs that together cause a substantial reduction in fitness...
  2. pmc SIFT: Predicting amino acid changes that affect protein function
    Pauline C Ng
    Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N A1 162, Seattle, WA 98109, USA
    Nucleic Acids Res 31:3812-4. 2003
    ..SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study...
  3. pmc Predicting deleterious amino acid substitutions
    P C Ng
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genome Res 11:863-74. 2001
    ..Each amino acid substitution potentially affects protein function...
  4. pmc Codon-substitution models for heterogeneous selection pressure at amino acid sites
    Z Yang
    Department of Biology, University College London, London NW1 2HE, United Kingdom
    Genetics 155:431-49. 2000
    ..However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets...
  5. ncbi TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis
    Jemeen Sreedharan
    Department of Clinical Neuroscience, King s College London, Medical Research Council MRC Centre for Neurodegeneration Research, and Institute of Psychiatry, London, SE5 8AF, UK
    Science 319:1668-72. 2008
    ..Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS...
  6. ncbi A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process
    Nicolas Lartillot
    Canadian Institute for Advanced Research, Departement de Biochimie, Universite de Montreal, Montreal, Quebec Canada
    Mol Biol Evol 21:1095-109. 2004
    ....
  7. pmc SNAP: predict effect of non-synonymous polymorphisms on function
    Yana Bromberg
    Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th St, New York, NY 10032, USA
    Nucleic Acids Res 35:3823-35. 2007
    ..This measure will allow users to focus on the most accurate predictions and/or the most severe effects. Available at http://www.rostlab.org/services/SNAP...
  8. ncbi The evolutionary fate and consequences of duplicate genes
    M Lynch
    Department of Biology, University of Oregon, Eugene, OR 97403, USA
    Science 290:1151-5. 2000
    ..Although duplicate genes may only rarely evolve new functions, the stochastic silencing of such genes may play a significant role in the passive origin of new species...
  9. pmc Automated inference of molecular mechanisms of disease from amino acid substitutions
    Biao Li
    School of Informatics and Computing, Indiana University, Bloomington, IN 47408, USA
    Bioinformatics 25:2744-50. 2009
    ..Although these methods are useful in practice, and accurate for their intended purpose, they are not well suited for providing probabilistic estimates of the underlying disease mechanism...
  10. pmc Assessing the evolutionary impact of amino acid mutations in the human genome
    Adam R Boyko
    Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA
    PLoS Genet 4:e1000083. 2008
    ....
  11. ncbi Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins
    Ana Maria Fernandez-Escamilla
    Nat Biotechnol 22:1302-6. 2004
    ..Furthermore, the algorithm opens the door to a fully automated, sequence-based design strategy to improve the aggregation properties of proteins of scientific or industrial interest...
  12. ncbi Predicting the effects of amino acid substitutions on protein function
    Pauline C Ng
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Annu Rev Genomics Hum Genet 7:61-80. 2006
    ..Here we provide an overview of amino acid substitution (AAS) prediction methods, which use sequence and/or structure to predict the effect of an AAS on protein ..
  13. pmc Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral
    S V Tavtigian
    International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon, France
    J Med Genet 43:295-305. 2006
    ..However, clinical testing methods with high sensitivity for deleterious mutations in these genes also detect many unclassified variants, primarily missense substitutions...
  14. ncbi Evolutionary rate in the protein interaction network
    Hunter B Fraser
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Science 296:750-2. 2002
    ..We confirm one predicted outcome of this process-namely, that interacting proteins evolve at similar rates...
  15. ncbi Adaptive protein evolution in Drosophila
    Nick G C Smith
    Centre for the Study of Evolution and School of Biological Sciences, University of Sussex, Brighton BN1 9QG, UK
    Nature 415:1022-4. 2002
    ..yakuba. We estimate that 45% of all amino-acid substitutions have been fixed by natural selection, and that on average one adaptive substitution occurs every 45 years in these species...
  16. ncbi The distribution of fitness effects of new mutations
    Adam Eyre-Walker
    Centre for the Study of Evolution, University of Sussex, Brighton, BN1 9QG, UK
    Nat Rev Genet 8:610-8. 2007
    ....
  17. pmc Genome wide analyses reveal little evidence for adaptive evolution in many plant species
    Toni I Gossmann
    Centre for the Study of Evolution, School of Life Sciences, University of Sussex, Brighton, United Kingdom
    Mol Biol Evol 27:1822-32. 2010
    ..We observe very similar results in all species; we find little evidence of adaptive amino acid substitution in any comparison except sunflowers...
  18. ncbi Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans
    Katia Koelle
    Department of Ecology and Evolutionary Biology, 2019 Kraus Natural Science Building, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109 1048, USA
    Science 314:1898-903. 2006
    ..It captures the observed boom-and-bust pattern of viral evolution, with periods of antigenic stasis during which genetic diversity grows, and with episodic contraction of this diversity during cluster transitions...
  19. pmc Complement factor H polymorphism in age-related macular degeneration
    Robert J Klein
    Laboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 308:385-9. 2005
    ..This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies...
  20. ncbi Estimating the rate of adaptive molecular evolution in the presence of slightly deleterious mutations and population size change
    Adam Eyre-Walker
    Centre for the Study of Evolution and School of Life Sciences, University of Sussex, Brighton, United Kingdom
    Mol Biol Evol 26:2097-108. 2009
    ....
  21. ncbi COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor
    Jon Kar Zubieta
    Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109 0720, USA
    Science 299:1240-3. 2003
    ..The COMT val158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli...
  22. pmc A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41
    Melody R Davis
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232 2363, USA
    J Virol 80:2405-17. 2006
    ..Our results suggest that an altered interaction between the MA domain of Gag and the gp41 cytoplasmic tail leads to dissociation of gp120 from gp41 during HIV-1 particle assembly, thus resulting in impaired fusion and infectivity...
  23. ncbi Mapping the antigenic and genetic evolution of influenza virus
    Derek J Smith
    Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK
    Science 305:371-6. 2004
    ..Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution...
  24. ncbi Loss of protein structure stability as a major causative factor in monogenic disease
    Peng Yue
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, MD 20850, USA
    J Mol Biol 353:459-73. 2005
    The most common cause of monogenic disease is a single base DNA variant resulting in an amino acid substitution. In a previous study, we observed that a high fraction of these substitutions appear to result in reduction of stability of ..
  25. pmc SNAP predicts effect of mutations on protein function
    Yana Bromberg
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
    Bioinformatics 24:2397-8. 2008
    ..Each prediction is associated with a reliability index that correlates with accuracy and thereby enables experimentalists to zoom into the most promising predictions...
  26. pmc Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus
    Yan Liu
    The Glycosciences Laboratory, Department of Medicine, Imperial College London, UK
    J Virol 84:12069-74. 2010
    ..These features of 222G mutants may contribute to exacerbation of disease...
  27. ncbi Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels
    Martin Tristani-Firouzi
    Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
    J Biol Chem 277:18994-9000. 2002
    ..Moreover, our findings suggest that the C-terminal ends of S4 and S6 are in close proximity at hyperpolarized membrane potentials...
  28. pmc Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog
    S R Hubbard
    Department of Pharmacology and Skirball Institute of Biomolecular Medicine, 540 First Avenue, New York University Medical Center, New York, NY 10016, USA
    EMBO J 16:5572-81. 1997
    ..The structure thus reveals the molecular basis for insulin receptor activation via autophosphorylation, and provides insights into tyrosine kinase substrate specificity and the mechanism of phosphotransfer...
  29. ncbi Kinase activity is required for the toxic effects of mutant LRRK2/dardarin
    Elisa Greggio
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892 3707, USA
    Neurobiol Dis 23:329-41. 2006
    ..We also show that dardarin protein is expressed within human midbrain neurons and that C-terminal epitopes are also found in some Lewy bodies...
  30. pmc Evidence for pervasive adaptive protein evolution in wild mice
    Daniel L Halligan
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    PLoS Genet 6:e1000825. 2010
    ..Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans...
  31. ncbi Accuracy and power of bayes prediction of amino acid sites under positive selection
    Maria Anisimova
    Department of Biology, Galton Laboratory, University College London, United Kingdom
    Mol Biol Evol 19:950-8. 2002
    ....
  32. pmc The distribution of fitness effects of new deleterious amino acid mutations in humans
    Adam Eyre-Walker
    School of Life Sciences, University of Sussex, Brighton, UK
    Genetics 173:891-900. 2006
    ....
  33. pmc Phenotypic characterization of resistant Val36 variants of hepatitis C virus NS3-4A serine protease
    Yi Zhou
    Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA 02139, USA
    Antimicrob Agents Chemother 52:110-20. 2008
    ..Finally, the sensitivity of these replicon variants to alpha interferon or ribavirin remained unchanged compared to that of the wild-type...
  34. ncbi Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 1b high viral load and non-virological response to interferon-ribavirin combination therapy
    Norio Akuta
    Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
    Intervirology 48:372-80. 2005
    ..Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs...
  35. ncbi Predicting the evolution of human influenza A
    R M Bush
    Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697, USA
    Science 286:1921-5. 1999
    ..However, not all codons in these sites had predictive value. Monitoring new H3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drift...
  36. ncbi Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6
    J A Ballesteros
    Novasite Pharmaceuticals, Inc, San Diego, California 92121, USA
    J Biol Chem 276:29171-7. 2001
    ..49), Arg(3.50), and Glu(6.30) may constitute a common switch governing the activation of many rhodopsin-like G-protein-coupled receptors...
  37. pmc Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis
    Shunsuke Kato
    Department of Clinical Oncology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980 8575, Japan
    Proc Natl Acad Sci U S A 100:8424-9. 2003
    ..This high-resolution mutation analysis allows evaluation of previous predictions and hypotheses through interrelation of function, structure and mutation...
  38. ncbi The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology
    Lukas Pezawas
    Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892 1379, USA
    J Neurosci 24:10099-102. 2004
    ....
  39. pmc Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus
    Viviane F Botosso
    Butantan Institute, Virology Branch, Butanta, Sao Paulo, Brazil
    PLoS Pathog 5:e1000254. 2009
    ....
  40. ncbi Genome-wide evidence for efficient positive and purifying selection in Capsella grandiflora, a plant species with a large effective population size
    Tanja Slotte
    Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada
    Mol Biol Evol 27:1813-21. 2010
    ..In particular, few studies have found convincing evidence for adaptive amino acid substitution in plants...
  41. pmc Pervasive cryptic epistasis in molecular evolution
    Mark Lunzer
    Biotechnology Institute, University of Minnesota, St Paul, Minnesota, USA
    PLoS Genet 6:e1001162. 2010
    ..This demonstrates that epistatic interactions can occur between distant (>20Å) sites. Phylogenetic analysis shows that incompatible mutations were fixed in different lineages...
  42. pmc Joint inference of the distribution of fitness effects of deleterious mutations and population demography based on nucleotide polymorphism frequencies
    Peter D Keightley
    Institute of Evolutionary Biology, University of Edinburgh, United Kingdom
    Genetics 177:2251-61. 2007
    ....
  43. ncbi Different trajectories of parallel evolution during viral adaptation
    H A Wichman
    Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA
    Science 285:422-4. 1999
    ..However, the order of these changes differed between replicates, and parallel substitutions did not reflect the changes with the largest beneficial effects or indicate a common trajectory of adaptation...
  44. pmc Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity
    Eric A Stone
    Department of Statistics, Stanford University, Stanford, California 94305 5324, USA
    Genome Res 15:978-86. 2005
    ....
  45. ncbi Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
    G C Kujoth
    Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53706, USA
    Science 309:481-4. 2005
    ..The levels of apoptotic markers were also found to increase during aging in normal mice. Thus, accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging...
  46. pmc R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice
    Youren Tong
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:14622-7. 2009
    ..Together, our data suggest that the R1441C mutation in LRRK2 impairs stimulated dopamine neurotransmission and D2 receptor function, which may represent pathogenic precursors preceding dopaminergic degeneration in PD brains...
  47. ncbi The molecular basis of mouse adaptation by human enterovirus 71
    Beng Hooi Chua
    Division of Virology, Telethon Institute for Child Health Research, Perth, Australia
    J Gen Virol 89:1622-32. 2008
    ..CHO-26M harboured a single mutation within the open reading frame (ORF), resulting in an amino acid substitution of K(149)-->I in the VP2 capsid protein; two further ORF mutations that resulted in amino acid ..
  48. pmc A single amino acid substitution in the West Nile virus nonstructural protein NS2A disables its ability to inhibit alpha/beta interferon induction and attenuates virus virulence in mice
    Wen Jun Liu
    School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, Australia
    J Virol 80:2396-404. 2006
    ..protein NS2A is a major inhibitor of IFN-beta promoter-driven transcription and that a single amino acid substitution in NS2A (Ala30 to Pro [A30P]) dramatically reduced its inhibitory effect (W. J. Liu, H. B. Chen, X. J...
  49. ncbi Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function
    Tong Xi
    Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
    Genomics 83:970-9. 2004
    Over 520 different amino acid substitution variants have been previously identified in the systematic screening of 91 human DNA repair genes for sequence variation...
  50. pmc Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants
    Xianting Li
    Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, USA
    J Neurochem 103:238-47. 2007
    ..The distinctive levels of kinase/GTPase activity in brain LRRK2 may help explain LRRK2-associated neuronal functions or dysfunctions in the pathogenesis of PD...
  51. pmc A three-state prediction of single point mutations on protein stability changes
    Emidio Capriotti
    Structural Genomics Unit, Bioinformatics Department, Centro de Investigación Príncipe Felipe CIPF, Valencia, Spain
    BMC Bioinformatics 9:S6. 2008
    ..0 kcal/mol), stabilizing mutations (DeltaDeltaG>1.0 kcal/mole) and neutral mutations (-1.0</=DeltaDeltaG</=1.0 kcal/mole)...
  52. ncbi rtREV: an amino acid substitution matrix for inference of retrovirus and reverse transcriptase phylogeny
    Matthew W Dimmic
    Biophysics Research Division, University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109 1055, USA
    J Mol Evol 55:65-73. 2002
    ..We provide evidence that rtREV is a more realistic evolutionary model for analyses of the pol gene, although it is inapplicable to analyses involving the gag gene...
  53. pmc Comparing models of evolution for ordered and disordered proteins
    Celeste J Brown
    Department of Biological Sciences, University of Idaho, USA
    Mol Biol Evol 27:609-21. 2010
    ..The highest correlations were observed between the amino acid frequencies in disordered proteins and the solvent-exposed loops and turns of ordered proteins, supporting an emerging structural model for disordered proteins...
  54. ncbi A combined empirical and mechanistic codon model
    Adi Doron-Faigenboim
    Department of Cell Research and Immunology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel
    Mol Biol Evol 24:388-97. 2007
    ..Using the suggested model, we further analyze human immunodeficiency virus type 1 protease sequences obtained from drug-treated patients and reveal positive selection in sites that are known to confer drug resistance to the virus...
  55. ncbi A photoactivatable GFP for selective photolabeling of proteins and cells
    George H Patterson
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Science 297:1873-7. 2002
    ..Here, we use the photoactivatable GFP both as a free protein to measure protein diffusion across the nuclear envelope and as a chimera with a lysosomal membrane protein to demonstrate rapid interlysosomal membrane exchange...
  56. pmc Entomologic and virologic investigation of Chikungunya, Singapore
    Lee Ching Ng
    National Environment Agency, Singapore
    Emerg Infect Dis 15:1243-9. 2009
    ..These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas...
  57. ncbi The biochemical architecture of an ancient adaptive landscape
    Mark Lunzer
    Biotechnology Institute, Evolution and Behavior, University of Minnesota, St Paul, MN 55108, USA
    Science 310:499-501. 2005
    ..The genotype-phenotype-fitness map shows that NAD use is a global optimum...
  58. ncbi C4 Photosynthesis evolved in grasses via parallel adaptive genetic changes
    Pascal Antoine Christin
    Department of Ecology and Evolution, Biophore, University of Lausanne, 1015 Lausanne, Switzerland
    Curr Biol 17:1241-7. 2007
    ..The C4-specific amino acids detected must be essential for C4 PEPC enzymatic characteristics, and their identification opens new avenues for the engineering of the C4 pathway in crops...
  59. pmc Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics
    Philippe Lemey
    Department of Zoology, University of Oxford, Oxford, United Kingdom
    PLoS Comput Biol 3:e29. 2007
    ....
  60. ncbi Empirical profile mixture models for phylogenetic reconstruction
    Le Si Quang
    Méthodes et Algorithmes pour la Bioinformatique, LIRMM, CNRS UM2, Montpellier Cedex 5, France
    Bioinformatics 24:2317-23. 2008
    ..In addition, these mixture models only perform well on large alignments, from which they can reliably learn the shapes of profiles, and their associated weights...
  61. ncbi Mutations in VP2 and VP1 capsid proteins increase infectivity and mouse lethality of enterovirus 71 by virus binding and RNA accumulation enhancement
    Sheng Wen Huang
    The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan
    Virology 422:132-43. 2012
    ..In sum, VP2(149M) and VP1(145E) mutations cooperatively promote viral binding and RNA accumulation of EV71, contributing to viral infectivity in vitro and mouse lethality in vivo...
  62. ncbi Identification of a point mutation in the voltage-gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids
    H Ranson
    Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
    Insect Mol Biol 9:491-7. 2000
    ..The An. gambiae sodium channel was physically mapped to chromosome 2L, division 20C. This position corresponds to the location of a major quantitative trait locus determining resistance to permethrin in the Kenyan strain of An. gambiae...
  63. ncbi Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database
    S E A Leigh
    Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, The Rayne Building, Royal Free and University College London Medical School, London WC1E 6JJ, UK
    Ann Hum Genet 72:485-98. 2008
    ....
  64. pmc The Escherichia coli GTPase CgtAE is involved in late steps of large ribosome assembly
    Mengxi Jiang
    Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 North University, Ann Arbor, MI 48109 1048, USA
    J Bacteriol 188:6757-70. 2006
    ..Finally, CgtA(E) cofractionates with the mature 50S but not with intermediate particles accumulated in other large ribosome assembly mutants...
  65. ncbi Activation of the OxyR transcription factor by reversible disulfide bond formation
    M Zheng
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Science 279:1718-21. 1998
    ..The redox potential of OxyR was determined to be -185 millivolts, ensuring that OxyR is reduced in the absence of stress. These results represent an example of redox signaling through disulfide bond formation and reduction...
  66. pmc Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals
    M Matrosovich
    Department of Virology and Molecular Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, Russia
    J Virol 74:8502-12. 2000
    ....
  67. ncbi The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA
    Andrew J Barbera
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Science 311:856-61. 2006
    ..Our findings present a paradigm for how nucleosomes may serve as binding platforms for viral and cellular proteins and reveal a previously unknown mechanism for KSHV latency...
  68. pmc Phylodynamic reconstruction reveals norovirus GII.4 epidemic expansions and their molecular determinants
    J Joukje Siebenga
    National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands
    PLoS Pathog 6:e1000884. 2010
    ..The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern...
  69. pmc Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model
    Minetaro Arita
    Department of Virology II, National Institute of Infectious Diseases, 4 7 1 Gakuen, Musashimurayama shi, Tokyo 208 0011, Japan
    J Virol 82:1787-97. 2008
    ..These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71...
  70. ncbi Rates of conservative and radical nonsynonymous nucleotide substitutions in mammalian nuclear genes
    J Zhang
    Institute of Molecular Evolutionary Genetics, Pennsylvania State University, University Park 16802, USA
    J Mol Evol 50:56-68. 2000
    ..An amino acid substitution can be classified as either conservative or radical, depending on whether it involves a change in a ..
  71. ncbi Selecton: a server for detecting evolutionary forces at a single amino-acid site
    Adi Doron-Faigenboim
    Department of Cell Research and Immunology, George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel
    Bioinformatics 21:2101-3. 2005
    ..We test for the statistical significance of the site-specific scores in order to obtain reliable and valid estimates...
  72. ncbi PMUT: a web-based tool for the annotation of pathological mutations on proteins
    Carles Ferrer-Costa
    Molecular Modeling and Bioinformatics Unit, Institut de Recerca Biomèdica, Parc Científic de Barcelona Josep Samitier 1 5, Barcelona 08028, Spain
    Bioinformatics 21:3176-8. 2005
    ..A graphical interface for Protein Data Bank (PDB) structures, when available, and a database containing hot spot profiles for all non-redundant PDB structures are also accessible from the PMUT server...
  73. pmc PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells
    Kendra A Bussey
    Department of Microbiology and Immunology, University of Rochester School of Medicine, 601 Elmwood Ave, Box 672, Rochester, NY 14642, USA
    J Virol 84:4395-406. 2010
    ..Our results clearly indicate the contribution of PB2 amino acid 271 to enhanced polymerase activity and viral growth in mammalian hosts...
  74. ncbi Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin
    Norio Akuta
    Department of Hepatology, Toranomon Hospital, Tokyo, Japan
    Hepatology 52:421-9. 2010
    ..In the patients having genotype non-TT, those of Arg70 gained high sustained virological response (50%), and sustained virological response (12%) was the worst in patients who possessed both genotype non-TT and Gln70(His70)...
  75. pmc A single amino acid of the human immunodeficiency virus type 2 capsid affects its replication in the presence of cynomolgus monkey and human TRIM5alphas
    Haihan Song
    Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    J Virol 81:7280-5. 2007
    ..Mutagenesis studies indicated that the single amino acid at the 120th position indeed affected the sensitivity of the virus to CM TRIM5alpha...
  76. ncbi A generation time effect on the rate of molecular evolution in invertebrates
    Jessica A Thomas
    Department of Ecology, Evolution and Natural Resources, Rutgers University, Cook Campus, USA
    Mol Biol Evol 27:1173-80. 2010
    ..We discuss both the practical and theoretical implications of these findings...
  77. pmc Structure of a KirBac potassium channel with an open bundle crossing indicates a mechanism of channel gating
    Vassiliy N Bavro
    Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK
    Nat Struct Mol Biol 19:158-63. 2012
    ....
  78. pmc Twelve positions in a β-lactamase that can expand its substrate spectrum with a single amino acid substitution
    Hyojeong Yi
    Department of Medicine, College of Medicine, Korea University, Seoul, Korea
    PLoS ONE 7:e37585. 2012
    ..These mapped substitutions represent a comprehensive set of general mechanical paths to substrate spectrum expansion in class A β-lactamases that all share a functional evolutionary mechanism using common conserved residues...
  79. ncbi A band 3-based macrocomplex of integral and peripheral proteins in the RBC membrane
    Lesley J Bruce
    Department of Biochemistry, University of Bristol, United Kingom
    Blood 101:4180-8. 2003
    ..We speculate that this macrocomplex may function as an integrated CO(2)/O(2) gas exchange unit (metabolon) in the erythrocyte...
  80. ncbi A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice
    Jason A Wicker
    Department of Microbiology and Immunology, Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases, and Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, TX 77555 0609, USA
    Virology 349:245-53. 2006
    ....
  81. ncbi Discriminative modelling of context-specific amino acid substitution probabilities
    Christof Angermüller
    Gene Center Munich and Department of Biochemistry, Ludwig Maximilians Universtät München, 81377 Munich, Germany
    Bioinformatics 28:3240-7. 2012
    ..This method showed drastically improved sensitivity and alignment quality compared with standard substitution matrix-based alignment...
  82. pmc Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance
    Rebecca E Symula
    Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America
    PLoS Negl Trop Dis 6:e1728. 2012
    ..In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function...
  83. pmc FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism
    Lijuan He
    Department of Materials Science and Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Biol Chem 286:13272-81. 2011
    ..These results further our knowledge of FGFR3-associated bone disorders...
  84. pmc Resistance to echinocandin-class antifungal drugs
    David S Perlin
    Public Health Research Institute, New Jersey Medical School UMDNJ, Newark, NJ, USA
    Drug Resist Updat 10:121-30. 2007
    ..and can account for intrinsic reduced susceptibility of certain species. Fks1 mutations confer resistance in both yeasts and moulds suggesting that this mechanism is pervasive in the fungal kingdom...
  85. pmc The N terminus of monoamine transporters is a lever required for the action of amphetamines
    Sonja Sucic
    Center of Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University Vienna, A 1090 Vienna, Austria
    J Biol Chem 285:10924-38. 2010
    ..Either modification abolished amphetamine-induced efflux. We therefore conclude that the N terminus of monoamine transporters acts as a lever that sustains reverse transport...
  86. pmc Defining structural and functional dimensions of the extracellular thyrotropin receptor region
    Gunnar Kleinau
    Department for Structural Biology, Leibniz Institut fur Molekulare Pharmakologie, D 13125 Berlin, Germany
    J Biol Chem 286:22622-31. 2011
    ....
  87. pmc Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors
    Atsuko Hachiya
    Laboratory of Virus Immunology, Research Center for AIDS, Institute for Virus Research, Kyoto University, 53, Kawaramachi, Shogoin, Sakyo ku, Kyoto 606 8507, Japan
    J Virol 82:3261-70. 2008
    ..Our results further highlight the role of connection subdomain residues in drug resistance...
  88. ncbi The conserved glutamate (Glu136) in transmembrane domain 2 of the serotonin transporter is required for the conformational switch in the transport cycle
    Vladimir M Korkhov
    Institute of Pharmacology, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Währinger Strasse 13a, A 1090 Vienna, Austria
    J Biol Chem 281:13439-48. 2006
    ..Thus, in the absence of Glu136, the conformational equilibrium of SERT is shifted progressively (SERT-E136D > SERT-E136Q > SERT-E136A) to the inward facing conformation...
  89. ncbi Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation
    P R Szeszko
    Department of Psychiatry Research, The Zucker Hillside Hospital, North Shore Long Island Jewish Health System, Glen Oaks, NY, USA
    Mol Psychiatry 10:631-6. 2005
    ..These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers...
  90. pmc TDP-43 A315T mutation in familial motor neuron disease
    Michael A Gitcho
    Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 63:535-8. 2008
    ..The discovery of a missense mutation in TDP-43 in a family with dominantly inherited motor neuron disease provides evidence of a direct link between altered TDP-43 function and neurodegeneration...
  91. pmc A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis
    Giuseppe di Fede
    Division of Neurology and Neuropathology, Carlo Besta National Neurological Institute, 20133 Milan, Italy
    Science 323:1473-7. 2009
    ....
  92. pmc HCV resistance to cyclosporin A does not correlate with a resistance of the NS5A-cyclophilin A interaction to cyclophilin inhibitors
    Udayan Chatterji
    The Scripps Research Institute, La Jolla, USA
    J Hepatol 53:50-6. 2010
    ..Recent studies showed that under Cyp inhibitor selection, mutations arose in the HCV nonstructural 5A (NS5A) protein. This led us to postulate that CypA assists HCV by acting on NS5A...
  93. ncbi Maximum likelihood methods for detecting adaptive evolution after gene duplication
    Joseph P Bielawski
    Department of Biology, University College London, Darwin Building, Gower Street, London WCIE 6BT, United Kingdom
    J Struct Funct Genomics 3:201-12. 2003
    ..We also comment on the limitations of these methods and discuss directions for further improvements...
  94. pmc Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus
    Erin M Sorrell
    Department of Veterinary Medicine, University of Maryland, College Park, and Virginia Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742, USA
    Proc Natl Acad Sci U S A 106:7565-70. 2009
    ..This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes...
  95. ncbi Quantifying the slightly deleterious mutation model of molecular evolution
    Adam Eyre-Walker
    Centre for the Study of Evolution and School of Biological Sciences, University of Sussex, Brighton BN1 9QG, UK
    Mol Biol Evol 19:2142-9. 2002
    ..Only approximately 10% or fewer of mutations seem to behave as SDMs, but SDMs could comprise a substantial fraction of mutations in protein-coding genes that have a chance of becoming fixed between species...
  96. pmc Using bioinformatics to predict the functional impact of SNVs
    Melissa S Cline
    Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, CA, USA
    Bioinformatics 27:441-8. 2011
    ..Here, we describe the essential components of bioinformatics tools that predict functional SNVs...
  97. pmc Dependence of leucine-rich repeat kinase 2 (LRRK2) kinase activity on dimerization
    Saurabh Sen
    Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Biol Chem 284:36346-56. 2009
    ....
  98. pmc Coding-sequence determinants of gene expression in Escherichia coli
    Grzegorz Kudla
    Department of Biology and Program in Applied Mathematics and Computational Science, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 324:255-8. 2009
    ..In our analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness...
  99. ncbi Genetic polymorphism of DNA base-excision repair genes (APE1, OGG1 and XRCC1) and their correlation with risk of lung cancer in a Chinese population
    Zheng Li
    Department of Pathology, Third Military Medical University, Chongqing, China
    Arch Med Res 42:226-34. 2011
    ..The aim of this study was to analyze the polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of lung cancer...
  100. pmc A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity
    Laurel Glaser
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Virol 79:11533-6. 2005
    ..Mutation of this single amino acid back to the avian consensus resulted in a preference for the avian receptor...
  101. ncbi Mapping abeta amyloid fibril secondary structure using scanning proline mutagenesis
    Angela D Williams
    Graduate School of Medicine, R221, University of Tennessee, 1924 Alcoa Highway, Knoxville, TN 37920, USA
    J Mol Biol 335:833-42. 2004
    ....

Research Grants63

  1. Enhanced iron removal with peptide linked chelators targeted to ferritin
    Elizabeth C Theil; Fiscal Year: 2010
    ..Moreover, amino acid substitution, mild heat, physiological concentrations of urea (1 mM) all unfold the ferritin pores to increase iron ..
  2. Genetics of the Neuromuscular Junction: Mechanisms and Disease Models
    Robert W Burgess; Fiscal Year: 2013
    ..We have demonstrated this using a mouse model of CMT2D, in which an amino acid substitution in GARS causes a dominant peripheral neuropathy despite normal enzymatic activity of the mutant protein, ..
  3. Non-viral gene therapy for sickle cell anemia
    CLIFFORD JOHN STEER; Fiscal Year: 2012
    ..cell anemia (SCA) is one of the most common inherited hematological diseases, and caused by a single amino acid substitution in the 2-globin chain of hemoglobin (Hb)...
  4. Adjunctive Use of Apyrase to Fibrinolytic Therapy
    Ridong Chen; Fiscal Year: 2013
    ..APT102 is an optimized human apyrase with two amino acid substitution that has significantly higher activity than the wild-type apyrases...
  5. Hunting for Endogenous Ligands for Invariant Natural Killer T Cells
    Peng George Wang; Fiscal Year: 2010
    ..domain of human iGb3S did not show any functional activity in synthesis of iGb3 due to at least one amino acid substitution. Despite the dispute of the existence of iGb3 in mice and human thymus samples or other tissues, the ..
  6. Structure/Function of Steroid Transforming AKR's
    Trevor M Penning; Fiscal Year: 2011
    ..We will test the hypothesis that a single amino acid substitution in the conserved AKR catalytic tetrad shifts the pKb of the catalytic tyrosine and this is responsible ..
  7. TYPE IV SECRETION &SIGNAL TRANSDUCTION IN EHRLICHIOSIS
    Yasuko Rikihisa; Fiscal Year: 2013
    ..transfected with wild-typeT4S effectors or mutant effectors with appropriate modifications (truncation, amino acid substitution, etc.). 2...
  8. Intragenic Suppressors of McCune-Albright Syndrome Mutations
    ROBIN PALS RYLAARSDAM; Fiscal Year: 2010
    ..A single amino acid substitution in the heterotrimeric G-protein subunit Gs causes constitutive activation of its signaling pathways, as ..
  9. Analysis of metallo-beta-lactamase sequence constraints at high resolution
    Timothy Palzkill; Fiscal Year: 2013
    ..This will allow an accurate estimate of the impact of any amino acid substitution at any active site residue on the substrate specificity and antibiotic resistance profile provided by an ..
  10. Neurovirulence of murine coronavirus: roles of viral genes
    Susan R Weiss; Fiscal Year: 2010
    ..30kDa protein encoded in ORF2a is specific to group 2 coronaviruses;we have recently observed that one amino acid substitution within this protein results in attenuation of recombinant MHV-A59...
  11. Interplay of Innate and Adaptive Immunity in Lupus Pathogenesis
    Michelle L Hermiston; Fiscal Year: 2013
    ..These mice express a single amino acid substitution that results in constitutive CD45 phosphatase activity...
  12. The Role of GPR54 Signaling in Pubertal Disorders
    SUZY DRUMOND CARVALHO BIANCO; Fiscal Year: 2010
    ..GPR54 is desensitized and internalized in response to continuous kisspeptin stimulation, and that a GPR54 amino acid substitution identified in a female patient with central precocious puberty (a disorder with disproportionately high ..
  13. Crohn's disease-associated NOD2 Mutants
    Xiaojing Ma; Fiscal Year: 2010
    ..frame shift mutation and the deletion of the terminal leucine-rich repeats (LRR) of the protein, and two amino acid substitution mutants also in the LRR region: R702W and G908R...
  14. The effect of pathological mutations in beta-III tubulin on microtubules and axon
    ADRIANNE LYNN KOLPAK; Fiscal Year: 2012
    ..model harboring the most common mutation identified in human CFEOM3 patients, and resulting in the R262C amino acid substitution, exhibits axon guidance defects without alterations in cortical architecture, suggesting this disease is ..
  15. Determinants of HIV Dynamics and Variation
    JOSE ORLANDO MALDONADO-ORTIZ; Fiscal Year: 2013
    ..F30 application proposes research that will thoroughly investigate the biological relevance of the A62V amino acid substitution in HIV-1 reverse transcriptase (RT)...
  16. Viral Constraints on SIV Escape from Cytotoxic T Lymphocytes
    WENDY WEN LI YEH; Fiscal Year: 2010
    ..an infected Mamu-A*01+ rhesus monkey is temporally correlated with the emergence of a flanking downstream amino acid substitution in the capsid protein. Our hypothesis is that the SHIV-89...
  17. Characterizing a novel hemophore from pathogenic and non-pathogenic mycobacteria.
    LISA M MCMATH; Fiscal Year: 2010
    ..BCG has an attenuated heme uptake pathway compared to Mtb, which may be, in part, attributed to a single amino acid substitution in the BCG hemophore...
  18. Genetic link between type 2 diabetes and atherosclerosis
    Weibin Shi; Fiscal Year: 2013
    ..There are multiple SNPs within the Hnf1a gene between B6 and BALB with one SNP in exon 9 leading to amino acid substitution. Recent genome- wide association studies have identified new loci that are implicated in [unreadable]-..
  19. Prevalence and immunogenicity of HNA-3a and -3b antibodies and antigens
    RICHARD HERBERT ASTER; Fiscal Year: 2012
    ..and that the HNA-3a/b polymorphism is almost certainly determined by an R>Q154 (R=HNA-3a, Q = HNA-3b) amino acid substitution in the first extracellular loop of the 10- membrane-spanning CTL2 protein...
  20. Regulation of glycogen metabolism: Insights from novel genetic models
    Molly E McCue; Fiscal Year: 2013
    ..gene encoding the skeletal muscle is form of glycogen synthase in horses with PSSM, which results in an amino acid substitution in a highly conserved region of the enzyme...
  21. Regulation of nitrogen catabolic gene expression in S. cerevisiae
    Terrance G Cooper; Fiscal Year: 2013
    ..The research strategy achieves this goal using gln3 amino acid substitution mutants that genetically isolate the hypothesized pathways from one another, thereby permitting one ..
  22. Ethanol sensitivity in delta subunit-containing GABA(A) receptors
    Martin Wallner; Fiscal Year: 2010
    ..The grant is organized into three aims. Aim 1 proposes to make use of a novel "functional tag", a single amino acid substitution in the d subunit, which renders it sensitive to benzodiazepines...
  23. Improved mutant meningococcal factor H binding protein vaccines
    PETER TRIP BEERNINK; Fiscal Year: 2013
    ..A single amino acid substitution in fHbp eliminated fH binding and increased the protective responses...
  24. Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3
    Beth A McCormick; Fiscal Year: 2013
    ..The caspase-3 cleavage motif is physiologically significant, as a single amino acid substitution to a sequence not recognized by CASP3 profoundly attenuates the virulence of this pathogen in both in ..
  25. Computational system to predict novel genetic disease associations
    MARK DOUGLAS YANDELL; Fiscal Year: 2010
    ..Given the prevalence of CVD in the developed world, these products are potentially a great boon to public health, as well as being significant commercial opportunities. ..
  26. Genetic and anatomic basis of the fibrosis syndromes
    Elizabeth C Engle; Fiscal Year: 2011
    ..Aim 3: Define the cellular consequences of the R954W amino acid substitution on the developing and mature ocular motor axis in mice. Aim 4: Identify KIF21A protein binding partners...
  27. NIH Genetic Aspects of Immunodeficiency
    Mary Ellen Conley; Fiscal Year: 2010
    ..Like the patients with mutations in Btk, a patient with an amino acid substitution in Ig? and a patient with a defect in BLNK had a small number of B cells in the blood with decreased ..
  28. LRRK2 and RhoGTPases: Local translation in neurodegeneration
    Diane Chan; Fiscal Year: 2012
    ..Investigation of the function of LRRK2 interactions with Rho GTPases may serve as a novel avenue for the development of disease-modifying therapeutics for the treatment of Parkinson's disease. ..
  29. BIOMATHEMATICAL ANALYSIS OF VIRAL DYNAMICS AND EVOLUTION
    Sergei L Kosakovsky Pond; Fiscal Year: 2012
    ..A key deliverable of the project will be open-source software tools that address the unique statistical analysis, interpretation and data access needs of this and similar projects working with HIV and other rapidly evolving pathogens. ..
  30. Critical domains for HIV-1 entry through atypical coreceptor usage
    Feng Gao; Fiscal Year: 2013
    ..In addition, it is striking that a single amino acid substitution at the V3 crown tip leads to significantly altered coreceptor usage in different virus backbones...
  31. TEST OF NEUTRAL MOLECULAR EVOLUTION
    Martin Kreitman; Fiscal Year: 1999
    ..12 proximal genes and 12 distal genes within the inversion will be sequenced, and rates of amino acid substitution of the same genes that have experienced different effective population sizes in the two species will be ..
  32. FUNCTIONAL ANALYSIS OF NOVEL GABA RECEPTOR IN DROSOPHILA
    Richard ffrench Constant; Fiscal Year: 1999
    ..He has identified a single amino acid substitution (alanine 302>serine) in Rdl, which confers resistance to cyclodienes and PTX...
  33. Byologic: Software for Mass Spectrometric Protein Drug Assays
    YONG JOO KIL; Fiscal Year: 2012
    ..Better characterized protein drugs will lead to better quality assurance, enhanced public safety, more informed regulatory decisions, and lower overall costs. ..
  34. Structure and Dynamics of the Synaptonemal Complex
    AMY JOY MACQUEEN; Fiscal Year: 2013
    ..Each zip1 allele represents a single amino acid substitution at the extreme C terminus of Zip1 and may reveal aspects of the mechanism underlying Zip1 assembly...
  35. Genome-wide prediction and analysis of coding variants
    Agnes Chan; Fiscal Year: 2011
    ..to be directly linked with human disease, 57% are based on mutations that encode a single nonsynonymous amino acid substitution in the corresponding protein...
  36. Identification and in vitro experimental investigation of missense SNPs implicate
    John Moult; Fiscal Year: 2013
    ..This project focuses on the role of missense SNPs (those that result in an amino acid substitution in a protein) in disease mechanism...
  37. Quorum-sensing mechanisms of Campylobacter
    PAUL PLUMMER; Fiscal Year: 2009
    ..designed and conducted by the principal investigator, this study will 1) determine the effect of the G92D amino acid substitution on the enzymatic activity of the C...
  38. CYP1A1 GENOTYPE & INDUCIBIL PHENOTYPE-HUM LUNG CA RISK
    Jennifer Hu; Fiscal Year: 1992
    ..This novel point mutation in genotype results in an amino acid substitution, which might affect enzyme inducibility phenotype and an individual's risk for oncogenic carcinoma...
  39. HUMAN MULTIDRUG RESISTANCE--PGLYCOPROTEIN GENES
    IGOR RONINSON; Fiscal Year: 1992
    ..different drugs was found in one case to result from point mutations in the mdrl gene leading to a single amino acid substitution in P-glycoprotein. Many aspects of P- glycoprotein function are poorly understood...
  40. SPATIOTEMPORAL ANALYSES OF NEONATAL HOST RESPONSE
    Christopher Contag; Fiscal Year: 2002
    ..Resistant and sensitive Nramp1 alleles, differing by a single amino acid substitution (G169D), have been identified in mice...
  41. Computational Investigations of Monomeric Variants of Red Fluorescent Proteins
    Prem P Chapagain; Fiscal Year: 2013
    ..Identifying these regions will permit a systematic computational-experimental strategy of amino acid substitution to create more protective proteins, and to modify the protein-chromophore interactions to enhance the ..
  42. MULTIPLE REPRESENTATIONS OF BIOLOGICAL SEQUENCES
    Douglas Brutlag; Fiscal Year: 1999
    ..We will use secondary-structure specific amino acid substitution matrices to provide specificity...
  43. ALPHA-1-PROTEINASE INHIBITOR DEFICIENCY AND EMPHYSEMA
    Savio Woo; Fiscal Year: 1990
    ..and analyzed the human Alpha1-antitrypsin cDNA and its corresponding gene, we demonstrated that the amino acid substitution is caused by a G to A transition at the corresponding position in the gene...
  44. NOVEL FAS BINDING PROTEIN AND ITS ROLE IN DISEASE
    Raif Geha; Fiscal Year: 1999
    ..A single amino acid substitution 238 Val-> Asn in the death domain of the intracellular region of Fas that abolishes Fas mediated ..
  45. DNA REPAIR GENOTYPE AND PHENOTYPE IN BREAST CANCER RISK
    Jennifer Hu; Fiscal Year: 2002
    ..Our working hypothesis is that polymorphism of DNA repair genes with nonconservative amino acid substitution may lead to altered protein function in DNA repair and elevated breast cancer risk...
  46. PHARMACOGENETICS OF PRO12ALA PPAR GAMMA 2 IN DIABETES
    ALAN SHULDINER; Fiscal Year: 2002
    ..In vitro studies indicate that this single amino acid substitution has functional consequences...
  47. Molecular Functions of the Adenovirus E1A Oncogene
    Maurice Green; Fiscal Year: 2006
    ..A large panel of EIA single amino acid substitution mutants will be used to define interactions among E1A, p300/CBP, and TBP and to establish their relevance ..
  48. CHARACTERIZATION OF HIV-1 IN SALIVA AND PLASMA
    Diane Shugars; Fiscal Year: 2001
    ..corresponding amino acid sequences of V3 products will be determined and classified as NSI or SI based on amino acid substitution pattern...
  49. BLOOD PLASMA PROTEINS--STRUCTURE AND FUNCTION
    Frank Putnam; Fiscal Year: 1993
    ..To date, the site of amino acid substitution has been determined in more than 25 different named specimens...
  50. HBF VARIANTS FOR GENE THERAPY OF SICKLE CELL DISEASE
    Kazuhiko Adachi; Fiscal Year: 2005
    ..with lower oxygen affinity than Hb S through not only enhancement of 2,3-BPG interaction but also amino acid substitution at the alyl interaction sites on the G helix...
  51. Clinical-Genetic Variation in GABA /Alcohol Sensitivity
    John Roache; Fiscal Year: 2004
    ..The polymorphism is a Proline to Serine amino acid substitution at position #385 (i.e., Pro385Ser)...
  52. MECHANISMS OF FIDELITY AND MUTAGENESIS
    Thomas Spratt; Fiscal Year: 2005
    ..The structure of the reactants will be altered by atomic substitution of the DNA and amino acid substitution of the polymerases, and the progress of the reaction will be measured with pre-steady-state kinetics...
  53. MECHANISMS OF RETROVIRUS INDUCED T AND NEURAL CELL DEATH
    Paul Wong; Fiscal Year: 2003
    ..A single amino acid substitution in the env gene of ts1 is responsible for inefficient transport of gPr80env from the endoplasmic ..
  54. Structures of the ends of telomeres
    MARTIN HORVATH; Fiscal Year: 2007
    ..Insights obtained from the proposed research will thus have significance for understanding human telomeres and the role that telomere structure plays in the biology of aging and cancer. [unreadable] [unreadable]..
  55. LIGAND/PROTEIN INTERACTIONS IN ESTROGEN RECEPTORS
    Richard Miksicek; Fiscal Year: 1993
    ..A systematic mutational analysis designed to introduce amino acid substitution-mutations throughout the carboxy terminal half of the receptor is proposed to generate refined functional ..
  56. MOLECULAR GENETIC ANALYSIS OF MYCOBACTERIUM TUBERCULOSIS
    William Jacobs; Fiscal Year: 2003
    ..They have also established a molecular basis for the attenuation of an M. bovis strain as due to an amino acid substitution in a principal sigma factor of RNA polymerase and have developed auxotrophic vaccine strains of BCG...
  57. Glutathione S-transferase polymorphisms in PARK1 parkin*
    Lawrence Golbe; Fiscal Year: 2003
    ..abstract_text> ..
  58. DMT1:Tissue specific expression & alternative splicing
    Martha Mims; Fiscal Year: 2006
    ..The human mutation predicts a conservative amino acid substitution, but its predominant effect is skipping of exon 12...
  59. STRUCTURAL ASPECTS OF ION CHANNEL FUNCTION
    Michael White; Fiscal Year: 1999
    ..Our approach is to create a series of predetermined single (or double) amino acid substitution mutants using site-directed mutagenesis, and then to compare the properties of the mutant receptors to ..
  60. High throughput screen for regulators of globin gene ex*
    Benjamin Ebert; Fiscal Year: 2006
    Sickle cell disease (SCD) is a common disease caused by a single amino acid substitution, ValSGIn, in the beta globin gene...
  61. ABCA1 knock-in mouse model to study molecular pathology of Alzheimer's Disease
    Iliya Lefterov; Fiscal Year: 2007
    ..Importantly, one of the primary ABCA1 mutant cell lines with a point mutation causing N935S amino acid substitution was established from a TD patient with dementia and abundant amyloid deposits in the brain, but without ..
  62. TRIPLEX BASED REPAIR OF THE SICKLE CELL MUTATION
    JACQUES FRESCO; Fiscal Year: 2003
    ..This malformation is the result of a single amino acid substitution (glutamic -> acid valine) at position 6 of the beta-globin chain, which, in turn, is due to an A ->..
  63. CD24 Polymorphism and multiple sclerosis
    Yang Liu; Fiscal Year: 2007
    ..Moreover, the human CD24 gene has a functional polymorphism due to a non-conserved amino acid substitution in a critical position of the CD24 protein...