isoaspartic acid

Summary

Summary: An ASPARTIC ACID residue in polypeptide chains that is linked at the beta-carboxyl group instead of at the normal, alpha-carboxyl group, polypeptide linkage. It is a result of the spontaneous decomposition of aspartic acid or ASPARAGINE residues.

Top Publications

  1. ncbi Formation, localization, and repair of L-isoaspartyl sites in histones H2A and H2B in nucleosomes from rat liver and chicken erythrocytes
    Wayne G Carter
    Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California 92697, USA
    Biochemistry 47:10757-64. 2008
  2. ncbi Biological significance of isoaspartate and its repair system
    Takahiko Shimizu
    Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
    Biol Pharm Bull 28:1590-6. 2005
  3. ncbi Structural integrity of histone H2B in vivo requires the activity of protein L-isoaspartate O-methyltransferase, a putative protein repair enzyme
    A L Young
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 276:37161-5. 2001
  4. ncbi Protein repair in the brain, proteomic analysis of endogenous substrates for protein L-isoaspartyl methyltransferase in mouse brain
    Jeff X Zhu
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 281:33802-13. 2006
  5. ncbi Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals?
    K J Reissner
    Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
    Cell Mol Life Sci 60:1281-95. 2003
  6. ncbi Isoaspartate-containing amyloid precursor protein-derived peptides alter efficacy and specificity of potential beta-secretases
    Livia Böhme
    Probiodrug AG, Biocenter, Weinbergweg 22, D 06120 Halle Saale, Germany
    Biol Chem 389:1055-66. 2008
  7. ncbi Folate status and age affect the accumulation of L-isoaspartyl residues in rat liver proteins
    Haifa Ghandour
    Vitamin Metabolism, Jean Mayer U S Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
    J Nutr 132:1357-60. 2002
  8. ncbi Spontaneous formation of L-isoaspartate and gain of function in fibronectin
    Flavio Curnis
    Department of Oncology, Cancer Immunotherapy and Gene Therapy Program and Italian Institute of Technology Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy
    J Biol Chem 281:36466-76. 2006
  9. ncbi Suppression of Bcl-xL deamidation in human hepatocellular carcinomas
    Tetsuo Takehara
    Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita 565 0871, Japan
    Cancer Res 63:3054-7. 2003
  10. pmc Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain
    Michael Bidinosti
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 285:19402-8. 2010

Scientific Experts

Detail Information

Publications157 found, 100 shown here

  1. ncbi Formation, localization, and repair of L-isoaspartyl sites in histones H2A and H2B in nucleosomes from rat liver and chicken erythrocytes
    Wayne G Carter
    Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California 92697, USA
    Biochemistry 47:10757-64. 2008
    ....
  2. ncbi Biological significance of isoaspartate and its repair system
    Takahiko Shimizu
    Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
    Biol Pharm Bull 28:1590-6. 2005
    ..We discuss here the pathological implications of the formation of isoaspartate in damaged proteins during neurodegeneration in model mice and AD...
  3. ncbi Structural integrity of histone H2B in vivo requires the activity of protein L-isoaspartate O-methyltransferase, a putative protein repair enzyme
    A L Young
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 276:37161-5. 2001
    ..The propensity of H2B to generate isoAsp in vivo may help explain why this histone in particular is found as a major antigen in autoimmune diseases such as lupus erythematosus...
  4. ncbi Protein repair in the brain, proteomic analysis of endogenous substrates for protein L-isoaspartyl methyltransferase in mouse brain
    Jeff X Zhu
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 281:33802-13. 2006
    ..Further study of the isoaspartate-prone proteins identified here may help elucidate the molecular basis of one or more developmental and/or age-related neurological diseases...
  5. ncbi Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals?
    K J Reissner
    Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
    Cell Mol Life Sci 60:1281-95. 2003
    ..Herein we describe the mechanism of Asx rearrangement, summarize the evidence that PIMT serves an important repair function, and then focus on emerging evidence that deamidation and isoAsp formation may sometimes have a useful function...
  6. ncbi Isoaspartate-containing amyloid precursor protein-derived peptides alter efficacy and specificity of potential beta-secretases
    Livia Böhme
    Probiodrug AG, Biocenter, Weinbergweg 22, D 06120 Halle Saale, Germany
    Biol Chem 389:1055-66. 2008
    ..While cathepsin B is more effective than BACE-1 in processing the Asp-containing peptide derivatives, only cathepsin B can cleave the isoAsp-containing peptides, which occurs with high catalytic efficiency...
  7. ncbi Folate status and age affect the accumulation of L-isoaspartyl residues in rat liver proteins
    Haifa Ghandour
    Vitamin Metabolism, Jean Mayer U S Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
    J Nutr 132:1357-60. 2002
    ..568). The importance of these observations is discussed...
  8. ncbi Spontaneous formation of L-isoaspartate and gain of function in fibronectin
    Flavio Curnis
    Department of Oncology, Cancer Immunotherapy and Gene Therapy Program and Italian Institute of Technology Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy
    J Biol Chem 281:36466-76. 2006
    ..Time-dependent generation of isoDGR may represent a sort of molecular clock for activating latent integrin binding sites in proteins...
  9. ncbi Suppression of Bcl-xL deamidation in human hepatocellular carcinomas
    Tetsuo Takehara
    Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita 565 0871, Japan
    Cancer Res 63:3054-7. 2003
    ..Thus, suppression of Bcl-xL deamidation may play a critical role in the regulation of cell death by apoptosis...
  10. pmc Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain
    Michael Bidinosti
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 285:19402-8. 2010
    ..Further, we show that 4E-BP2 containing isoaspartates lacks the augmented association with raptor that is a feature of deamidated 4E-BP2...
  11. ncbi Protein isoaspartate methyltransferase-mediated 18O-labeling of isoaspartic acid for mass spectrometry analysis
    Min Liu
    Analytical Research and Development, Amgen, One Amgen Center Drive, Thousand Oaks, California 91320, United States
    Anal Chem 84:1056-62. 2012
    Arising from spontaneous aspartic acid (Asp) isomerization or asparagine (Asn) deamidation, isoaspartic acid (isoAsp, isoD, or beta-Asp) is a ubiquitous nonenzymatic modification of proteins and peptides...
  12. ncbi Accumulation of altered aspartyl residues in erythrocyte proteins from patients with Down's syndrome
    Patrizia Galletti
    Department of Biochemistry and Biophysics, School of Medicine, Second University of Naples, Italy
    FEBS J 274:5263-77. 2007
    ..The possible pathophysiological implications are discussed...
  13. ncbi Isoaspartate residues dramatically influence substrate recognition and turnover by proteases
    Livia Böhme
    Probiodrug AG, Biocenter, Weinbergweg 22, D 06120 Halle Saale, Germany
    Biol Chem 389:1043-53. 2008
    ..In contrast, acylamino acid-releasing enzyme and dipeptidyl peptidases 1, 2 and 4 hydrolyzed substrates containing the isoAsp-Ala motif...
  14. ncbi Inactivation of epoxide hydrolase by catalysis-induced formation of isoaspartate
    Bert van Loo
    Biochemical Laboratory, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
    FEBS Lett 582:1581-6. 2008
    ..Inactivation occurred at a lower rate with the (S)-enantiomer of para-nitrostyrene epoxide, indicating that it is related to the structure of the covalent hydroxyalkyl-enzyme intermediate...
  15. ncbi Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells
    Stefania D'Angelo
    Department of Biochemistry and Biophysics F Cedrangolo, Medical School, Second University of Naples, Naples, Italy
    Free Radic Biol Med 38:908-19. 2005
    ....
  16. pmc Deamidation of asparagine in a major histocompatibility complex-bound peptide affects T cell recognition but does not explain type B reactivity
    T P Cirrito
    Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
    J Exp Med 194:1165-70. 2001
    ..A number of T cells recognize 48-61 with asparagine at position 59, but not the aspartic acid or isoaspartic acid derivatives...
  17. ncbi Crystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate
    S C Griffith
    Department of Chemistry and Biochemistry and Molecular Biology Institute, University of California, Los Angeles 90095 1569, USA
    J Mol Biol 313:1103-16. 2001
    ..Manual and computer-based docking studies on different isomers help explain how the enzyme uses steric effects to make the critical distinction between normal L-aspartyl and age-damaged L-isoaspartyl and D-aspartyl residues...
  18. ncbi Detection of isoAspartate residues as a posttranslational modification of proteins and peptides
    Verne Schirch
    Department of Biochemistry, Virginia Commonwealth University, Richmond, VA, USA
    Methods Mol Biol 194:269-76. 2002
  19. ncbi [Role of isomerized protein repair enzyme, PIMT, in cellular functions]
    Takemitsu Furuchi
    Sch of Pharmaceut Sci, Kitasato Univ, 5 9 1 Shirogane, Minato ku, Tokyo 108 8641, Japan
    Yakugaku Zasshi 127:1927-36. 2007
    ..These results indicate that the ability to repair L-isoaspartyl-(or D-aspartyl-) containing proteins is important for the maintenance of normal MEK-ERK signaling...
  20. ncbi Development of a strong cation-exchange high-performance liquid chromatography method for analysis of isoaspartate in proteins
    Wei Zhang
    Wyeth BioPharma, Genetics Institute Campus, Andover, MA 01810, USA
    Anal Biochem 307:184-6. 2002
  21. ncbi A failure to repair self-proteins leads to T cell hyperproliferation and autoantibody production
    Hester A Doyle
    Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 171:2840-7. 2003
    ..These observations, coupled with the fact that humans have polymorphisms in the pcmt gene, suggest that isoaspartyl self-proteins may alter the maintenance of peripheral immune tolerance...
  22. pmc Deamidation: Differentiation of aspartyl from isoaspartyl products in peptides by electron capture dissociation
    Jason J Cournoyer
    Mass Spectrometry Resource, Department of Biochemistry, Boston University School of Medicine, 715 Albany St, R806, Boston, MA 02118, USA
    Protein Sci 14:452-63. 2005
    ..b>Isoaspartic acid is an isomer of aspartic acid with the C(beta) incorporated into the backbone, thus increasing the length of ..
  23. pmc Selective cleavage of isoaspartyl peptide bonds by hydroxylamine after methyltransferase priming
    Jeff X Zhu
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA
    Anal Biochem 364:1-7. 2007
    ..Location of the isoAsp linkage is then inferred by identifying the cleavage products by mass spectrometry or N-terminal sequencing...
  24. ncbi Altered immunogenicity of isoaspartate containing proteins
    Hester A Doyle
    Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    Autoimmunity 40:131-7. 2007
    ..have found that one such post-translational modification, the spontaneous conversion of an aspartic acid to isoaspartic acid (isoAsp), causes ignored self-antigens to become immunogenic...
  25. ncbi Analysis of oxidative modification of proteins
    L J Yan
    Southern Methodist University, Dallas, Texas, USA
    Curr Protoc Protein Sci . 2001
    ..Such oxidatively modified products may also be used as biomarkers for the assessment of oxidative stress during aging and/or disease...
  26. ncbi Isoaspartyl post-translational modification triggers anti-tumor T and B lymphocyte immunity
    Hester A Doyle
    Yale University School of Medicine, New Haven, CT 06520, USA
    J Biol Chem 281:32676-83. 2006
    ..In particular, the conversion of an aspartic acid to an isoaspartic acid within the melanoma antigen tyrosinase-related protein (TRP)-2 peptide-(181-188) makes the otherwise ..
  27. ncbi Deamidation of labile asparagine residues in the autoregulatory sequence of human phenylalanine hydroxylase
    Therese Solstad
    Department of Biochemistry and Molecular Biology, Proteomic Unit, University of Bergen, Arstadveien 19, N 5009 Bergen, Norway
    Eur J Biochem 270:929-38. 2003
    ..isoaspartyl (isoAsp) was demonstrated in this 28-residue peptide by its methylation by protein-l-isoaspartic acid O-methyltransferase (PIMT; EC 2.1.1.77). Thirdly, on incubation at pH 7...
  28. ncbi Serum CrossLaps for monitoring the response in individuals undergoing antiresorptive therapy
    S Christgau
    Osteometer BioTech A S, Osteopark, Herlev, Denmark
    Bone 26:505-11. 2000
    ..In conclusion, the serum CTx showed high specificity and sensitivity for monitoring individual responses to antiresorptive therapy. More than 92% of the treated women showed significant responses in serum CTx measurements after 6 months...
  29. ncbi Membrane docking of an aggregation-prone protein improves its solubilization
    Jihen Tagourti
    Molecules de stress, Institut Jacques Monod, Universite Paris 7, 2, place Jussieu, 75005 Paris, France
    Gene 426:32-8. 2008
    ..Cross-linking experiments show that the inner membrane protein ChbC interacts with preS2-S'-beta-galactosidase. Our results suggest that membrane docking of aggregation-prone proteins might be a useful method for their solubilization...
  30. ncbi 18O labeling method for identification and quantification of succinimide in proteins
    Gang Xiao
    Department of Pharmaceutics, Amgen, Inc, Thousand Oaks, California 91320, USA
    Anal Chem 79:2714-21. 2007
    ..The method utilizes 18O water to monitor succinimide hydrolysis. 18O-labeled isoaspartic acid and aspartic acid peptides were produced by hydrolysis of a succinimide-containing protein in 18O water (..
  31. ncbi Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme
    Vasanthy Vigneswara
    Medical Research Council Applied Neuroscience Group, School of Biomedical Sciences, The University of Nottingham, Queen s Medical Centre, Nottingham NG7 2UH, United Kingdom
    J Biol Chem 281:32619-29. 2006
    ....
  32. pmc Biotechnological process for production of beta-dipeptides from cyanophycin on a technical scale and its optimization
    Ahmed Sallam
    Institut fur Molekulare Mikrobiologie und Biotechnologie, Westfalische Wilhelms Universitat Munster, D 48149 Munster, Germany
    Appl Environ Microbiol 75:29-38. 2009
    ..The optimized process was performed with industrial materials and equipment and is applicable to any desired scale...
  33. pmc ABRF ESRG 2005 study: identification of seven modified amino acids by Edman sequencing
    D Brune
    Arizona State University, Tempe, USA
    J Biomol Tech 17:308-26. 2006
    ..acids: dimethyl- and trimethyl-lysine, 3-methyl-histidine, N-carbamyl-lysine, cystine, N-methyl-alanine, and isoaspartic acid. The modified amino acids were interspersed with standard amino acids to help in the assessment of initial ..
  34. ncbi Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?
    A M Wagner
    Steno Diabetes Center, Niels Steensens Vej 2, Gentofte, 2820, Denmark
    Diabetologia 50:676-81. 2007
    ..The aim of this study was to assess the role of PIMT in the development of type 1 diabetes...
  35. ncbi Enzymatic hydrolysis of alpha- and beta-oligo(L-aspartic acid)s by poly(aspartic acid) hydrolases-1 and 2 from Sphingomonas sp. KT-1
    Tomohiro Hiraishi
    Polymer Chemistry Laboratory, RIKEN Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Macromol Biosci 4:330-9. 2004
    ....
  36. ncbi Methyl esterification of C-terminal leucine residues in cytosolic 36-kDa polypeptides of bovine brain. A novel eucaryotic protein carboxyl methylation reaction
    H Xie
    Department of Chemistry and Biochemistry, University of California, Los Angeles 90024
    J Biol Chem 268:13364-71. 1993
    ..These results provide evidence for a new type of reversible posttranslational modification reaction that may function to modulate the activities of its methyl-accepting substrates...
  37. ncbi Role of transmethylation reactions in alcoholic liver disease
    Kusum K Kharbanda
    Department of Veterans Affairs Medical Center, Research Service 151, 4101 Woolworth Avenue, Omaha, Nebraska 68105, USA
    World J Gastroenterol 13:4947-54. 2007
    ..In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse...
  38. ncbi The effect of urea exposure on isoaspartyl content and protein L-isoaspartate methyltransferase activity in Drosophila melanogaster
    C L David
    Department of Molecular Biology and Biochemistry, University of California, Irvine 92697 3900, USA
    Comp Biochem Physiol B Biochem Mol Biol 124:423-7. 1999
    ..The latter findings indicate that urea tolerance evolved in the selected populations without any significant change in PIMT expression or activity...
  39. pmc Structural investigation of a phosphorylation-catalyzed, isoaspartate-free, protein succinimide: crystallographic structure of post-succinimide His15Asp histidine-containing protein
    Scott Napper
    Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada
    Biochemistry 47:9486-96. 2008
    ..This is considerably significant for evaluation of protein stability and integrity...
  40. ncbi Deamidation of calmodulin at neutral and alkaline pH: quantitative relationships between ammonia loss and the susceptibility of calmodulin to modification by protein carboxyl methyltransferase
    B A Johnson
    School of Biological Sciences, University of California, Irvine 92717
    Arch Biochem Biophys 268:276-86. 1989
    ..A. Johnson, N. E. Freitag, and D. W. Aswad, (1985) J. Biol. Chem. 260, 10913-10916) that deamidation occurs preferentially at Asn-60 and/or Asn-97, each of which resides in a distinct Ca2+-binding domain...
  41. ncbi Microtubule-associated protein 1B binds glyceraldehyde-3-phosphate dehydrogenase
    Nathalie Cueille
    Département de Biologie Cellulaire et de Morphologie DBCM, Universite de Lausanne, 9 rue du Bugnon, 1005 Lausanne, Suisse
    J Proteome Res 6:2640-7. 2007
    ..GAPDH may be essential in the local energy provision of cytoskeletal structures and MAP1B may help to keep this key enzyme close to the cytoskeleton...
  42. ncbi Adenoviral expression of protein-L-isoaspartyl methyltransferase (PIMT) partially attenuates the biochemical changes in PIMT-deficient mice
    Midori Ogawara
    Department of Molecular Genetics, Tokyo Metropolitan Institute of Gerontology, Itabashi ku, Japan
    J Neurosci Res 69:353-61. 2002
    ..The results suggested a new reagent for gene therapy applicable to ageing-associated neurodegenerative disorders...
  43. ncbi Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice
    Christine E Farrar
    Department of Neurobiology, University of California, Los Angeles, Los Angeles, California 90095, USA
    J Comp Neurol 493:524-37. 2005
    ....
  44. ncbi Mechanism of asparagine deamidation during human senile cataractogenesis
    L Takemoto
    Division of Biology, Ackert Hall, Kansas State University, Manhattan, KS 66506, USA
    Exp Eye Res 72:559-63. 2001
    ....
  45. ncbi Overexpression of L-isoaspartate O-methyltransferase in Escherichia coli increases heat shock survival by a mechanism independent of methyltransferase activity
    Jason Kindrachuk
    Department of Biochemistryand Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada
    J Biol Chem 278:50880-6. 2003
    ..An alternate hypothesis as to the physiological substrate and function of L-isoaspartyl methyltransferase is proposed...
  46. pmc Substrates of the Arabidopsis thaliana protein isoaspartyl methyltransferase 1 identified using phage display and biopanning
    Tingsu Chen
    Department of Horticulture, University of Kentucky, Lexington, Kentucky 40546 0312, USA
    J Biol Chem 285:37281-92. 2010
    ..Impaired PIMT activity would hinder protein function in these targets, possibly resulting in poor seed performance...
  47. ncbi Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair
    M M Skinner
    Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
    Structure 8:1189-201. 2000
    ..Protein L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) is a conserved and nearly ubiquitous enzyme that catalyzes the repair of proteins damaged by isoaspartyl formation...
  48. pmc A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida
    Huiping Zhu
    Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, TX 77030, USA
    Mol Genet Metab 87:66-70. 2006
    ..6, 95% confidence interval: 0.4-0.9). Our results showed that the Ile120Val polymorphism of PCMT1 gene is a genetic modifier for the risk of spina bifida. Val/Val genotype was associated with a reduction in risk for spina bifida...
  49. ncbi Phenotypic analysis of seizure-prone mice lacking L-isoaspartate (D-aspartate) O-methyltransferase
    E Kim
    Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141 9100, USA
    J Biol Chem 274:20671-8. 1999
    ..Consistent with this concept, the growth rate of Pcmt1-/- fibroblasts was indistinguishable from that of wild-type fibroblasts...
  50. ncbi Deamidation of -Asn-Gly- sequences during sample preparation for proteomics: Consequences for MALDI and HPLC-MALDI analysis
    Oleg V Krokhin
    Manitoba Centre for Proteomics and Systems Biology, University of Manitoba 799 JBRC, 715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada
    Anal Chem 78:6645-50. 2006
    ..species are produced, one containing an aspartic acid (-Asp-Gly-) residue and the other containing an isoaspartic acid (-betaAsp-Gly-) residue. For the peptide SLNGEWR (54-60 beta-galactosidase, E...
  51. pmc A protein methyltransferase specific for altered aspartyl residues is important in Escherichia coli stationary-phase survival and heat-shock resistance
    C Li
    Department of Chemistry and Biochemistry, University of California, Los Angeles 90024 1569
    Proc Natl Acad Sci U S A 89:9885-9. 1992
    ..These results provide genetic evidence for a role of the L-isoaspartyl methyltransferase in the metabolism of altered proteins that can accumulate in aging cells and limit their viability...
  52. ncbi Characterization of asparagine deamidation and aspartate isomerization in recombinant human interleukin-11
    Wei Zhang
    Wyeth BioPharma, Genetics Institute Campus, Andover, Massachusetts 01810, USA
    Pharm Res 19:1223-31. 2002
    ..PURPOSE; The aim of this study was to investigate asparagine (Asn) deamidation and aspartate (Asp) isomerization and to measure the content of isoaspartate (isoAsp) in recombinant human interleukin-11 (rhIL-11)...
  53. ncbi Conformational variation revealed by the crystal structure of RNase U2A complexed with Ca ion and 2'-adenylic acid at 1.03 Å resolution
    Shuji Noguchi
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113 0033, Japan
    Protein Pept Lett 17:1559-61. 2010
    ..The structure suggests that in solution the region around Asn32-Gly33 is likely to be in equilibrium between multiple conformers, with the deamidation of Asn32 proceeding when the region adopts an extended conformation...
  54. ncbi Comparative X-ray analysis of the un-liganded fosfomycin-target murA
    S Eschenburg
    Max Planck Institute for Medical Research, Department of Biophysics, Heidelberg, Germany
    Proteins 40:290-8. 2000
    ..The homogeneous population with L-isoaspartate in both structures suggests that the modification in Enterobacter cloacae MurA is not a mere aging defect but rather the result of a specific in vivo process...
  55. ncbi Localization of biologically uncommon D-beta-aspartate-containing alphaA-crystallin in human eye lens
    N Fujii
    Research Reactor Institute, Kyoto University Kumatori, Sennan, Osaka, Japan
    Mol Vis 6:1-5. 2000
    ....
  56. ncbi Intracellular protein modification associated with altered T cell functions in autoimmunity
    Mei Ling Yang
    Section of Rheumatology, Department of Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520, USA
    J Immunol 177:4541-9. 2006
    ..These studies demonstrate a role for the accumulation of intracellular isoAsp proteins associated with T cell proliferative defects of MRL autoimmune mice...
  57. ncbi Formation of an RNase A derivative containing an aminosuccinyl residue in place of asparagine 67
    S Capasso
    Dipartimento di Scienze Ambientali, Seconda Universita di Napoli, Caserta, Italy
    Biopolymers 56:14-9. 2000
    At acidic pH, Asp67 and beta-Asp67 (beta-Asp: isoaspartic acid residue) derivatives of RNase A, obtained by selective deamidation of the parent enzyme, spontaneously produces a new derivative containing an aminosuccinyl residue (Asu)...
  58. pmc Deficiency of a protein-repair enzyme results in the accumulation of altered proteins, retardation of growth, and fatal seizures in mice
    E Kim
    The Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141 9100, USA
    Proc Natl Acad Sci U S A 94:6132-7. 1997
    ..These results suggest that the ability of mice to repair L-isoaspartyl- and D-aspartyl-containing proteins is essential for normal growth and for normal central nervous system function...
  59. pmc Analysis of isoaspartate in peptides by electrospray tandem mass spectrometry
    W D Lehmann
    Central Spectroscopy Unit, German Cancer Research Center DKFZ, Heidelberg, Germany
    Protein Sci 9:2260-8. 2000
    ..Thus, the analytical procedures described may be helpful for the identification of suspected Asn deamidation and Asp isomerization sites in proteolytic digests of proteins...
  60. ncbi Abeta species, including IsoAsp23 Abeta, in Iowa-type familial cerebral amyloid angiopathy
    Youngah Shin
    Alzheimer Research Unit, Massachusetts General Hospital, 114 16th St, Charlestown 02129, USA
    Acta Neuropathol 105:252-8. 2003
    ..These data suggest that alteration of Abeta Asn23 to isoAsp may be an important determinant in the deposition of Abeta in cerebral blood vessels...
  61. ncbi Characterization of new D-beta-aspartate-containing proteins in a lens-derived cell line
    Takumi Takata
    Research Reactor Institute, Kyoto University, Kumatori cho, Sennan, Osaka 590 0494, Japan
    Biochem Biophys Res Commun 334:1022-31. 2005
    ....
  62. ncbi Differential analysis of D-beta-Asp-containing proteins found in normal and infrared irradiated rabbit lens
    Takumi Takata
    Research Reactor Institute, Kyoto University, Kumatori cho, Sennan, Osaka 590 0494, Japan
    Biochem Biophys Res Commun 344:263-71. 2006
    ..Additionally, some d-beta-Asp-containing proteins only appear after IR irradiation. One such protein is the alpha-enolase, which shows homology to tau-crystallin...
  63. ncbi Sequence-specific predictive chromatography to assist mass spectrometric analysis of asparagine deamidation and aspartate isomerization in peptides
    Nadezda P Sargaeva
    Boston University School of Medicine, Boston, MA, USA
    Electrophoresis 32:1962-9. 2011
    ..In this work we extended recently introduced critical liquid chromatography of biomacromolecule model for prediction of RTs for peptides containing asparagines, aspartic acid, and isoaspartic acid residues.
  64. ncbi Analysis of oxidative modification of proteins
    Liang Jun Yan
    Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA
    Curr Protoc Protein Sci . 2009
    ..Finally, methods are described for the quantification of protein-bound isoaspartate using protein-L-isoaspartyl methyltransferase that converts aberrant L-isoaspartyl residues in peptides and proteins to normal aspartyl residues...
  65. ncbi Structural changes induced by the deamidation and isomerization of asparagine revealed by the crystal structure of Ustilago sphaerogena ribonuclease U2B
    Shuji Noguchi
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo ku, Tokyo 113 0033, Japan
    Biopolymers 93:1003-10. 2010
    ..The structure suggests that the deamidation of the Asn and the isoAsp formation in proteins could confer immunogenicity...
  66. ncbi iTRAQ quantitative clinical proteomics revealed role of Na(+)K(+)-ATPase and its correlation with deamidation in vascular dementia
    Sunil S Adav
    School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
    J Proteome Res 13:4635-46. 2014
    ..Our findings suggest impaired regulation and compromised activity of ion channel proteins contribute to the pathophysiology of VaD. ..
  67. ncbi Methylation of histone H4 at aspartate 24 by protein L-isoaspartate O-methyltransferase (PCMT1) links histone modifications with protein homeostasis
    Burcu Biterge
    1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U 964, Universite de Strasbourg, 67404 Illkirch, France 2 Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg im Breisgau, Germany 3 University of Freiburg, Fahnenbergplatz, 79085 Freiburg im Breisgau, Germany
    Sci Rep 4:6674. 2014
    ..Thus, this work links for the first time a histone modification with histone protein aging and histone homeostasis, suggesting novel functions for histone modifications beyond transcriptional regulation. ..
  68. ncbi Probing deamidation in therapeutic immunoglobulin gamma (IgG1) by 'bottom-up' mass spectrometry with electron transfer dissociation
    Raju Mukherjee
    Research and Development, Biocon Limited, 20th KM, Hosur Road, Bangalore 560100, India
    Rapid Commun Mass Spectrom 24:879-84. 2010
    Aspartic acid formed by nonenzymatic deamidation of asparagine often isomerizes to isoaspartic acid through a succinimide intermediate. Accumulation of isoaspartic acid initiates aggregation and degradation in proteins...
  69. pmc Glutamine deamidation: differentiation of glutamic acid and gamma-glutamic acid in peptides by electron capture dissociation
    Xiaojuan Li
    Mass Spectrometry Resource, Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Anal Chem 82:3606-15. 2010
    ..ECD) can be used to generate diagnostic ions for the deamidation products of Asn: aspartic acid (Asp) and isoaspartic acid (isoAsp)...
  70. ncbi New proteomic developments to analyze protein isomerization and their biological significance in plants
    Philippe Grappin
    Institut Jean Pierre Bourgin, UMR1318 INRA AgroParisTech, Institut National de la Recherche Agronomique, F 78026 Versailles Cedex, France
    J Proteomics 74:1475-82. 2011
    ..Extended use to Arabidopsis model systems is promising for the discovery of controlling mechanisms induced by these particular post-translational modifications and their biological role in plants...
  71. ncbi Unprecedented occurrence of isoaspartic acid in a plant cyclopeptide
    Damien Lacroix
    Molécules de Communication et Adaptation des Micro organismes, UMR 7245 CNRS, Museum national d histoire naturelle, 63 Rue Buffon 75005 Paris, France
    Org Lett 14:576-9. 2012
    ..Surprisingly, the sequence of cyclocitropside C differed from that of cyclocitropside B only by an Asp(5)/isoAsp(5) substitution. This is the first report of an isoAsp residue in a plant cyclic peptide...
  72. ncbi A quantitative analysis of spontaneous isoaspartate formation from N-terminal asparaginyl and aspartyl residues
    Bert H O Güttler
    Probiodrug AG, Weinbergweg 22, Biozentrum, 06120, Halle Saale, Germany
    Amino Acids 44:1205-14. 2013
    ..The study provides evidence for a spontaneous N-terminal isoAsp-formation within peptides and might explain the accumulation of N-terminal isoAsp in amyloid deposits...
  73. ncbi Localization of D-beta-aspartic acid-containing proteins in human eyes
    Yuichi Kaji
    Department of Ophthalmology, University of Tsukuba, Institute of Clinical Medicine, Ibaraki, Japan
    Invest Ophthalmol Vis Sci 48:3923-7. 2007
    ..To reveal the role of the D-beta-Asp formation in the aging process of eyes, immunohistochemical localization of D-beta-Asp was investigated in ocular samples of various ages...
  74. pmc Alcohol-related brain damage in humans
    Amaia M Erdozain
    School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom Department of Pharmacology, University of the Basque Country, and Centro de Investigación Biomédica en Red de Salud Mental, Spain
    PLoS ONE 9:e93586. 2014
    ..Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics. ..
  75. ncbi Chronoregulation by asparagine deamidation
    Steven J Weintraub
    Division of Urology, Department of Cell Biology and Physiology, The Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8242, St Louis, MO 63110, USA
    Sci STKE 2007:re7. 2007
    ..This characteristic, combined with the wide range of deamidation rates that can be programmed, imparts to asparagines the potential to serve as molecular timers that regulate protein function and stability...
  76. doi Analysis of oxidative modification of proteins
    Liang Jun Yan
    Southern Methodist University, Dallas, Texas, USA
    Curr Protoc Cell Biol . 2002
    ..Methods described in this unit include spectrophotometry, immunoblotting, radiolabeling, GC/MS, ELISA adapted for analysis of oxidative modification...
  77. ncbi Consequence of neo-antigenicity of the 'altered self'
    P Eggleton
    Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, Devon EX1 2LU, UK
    Rheumatology (Oxford) 47:567-71. 2008
    ..include: the induction of peptide immunogenicity by the spontaneous conversion of aspartic acid residues to isoaspartic acid; granzyme B-mediated cleavage of SLE autoantigens; the oxidative modification--on the surface of apoptotic ..
  78. pmc Integrated proteomic analysis of major isoaspartyl-containing proteins in the urine of wild type and protein L-isoaspartate O-methyltransferase-deficient mice
    Shujia Dai
    Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston Massachusetts 02115, United States
    Anal Chem 85:2423-30. 2013
    ..Additionally, the developed method opens up the possibility to explore processing mechanisms of isoaspartyl proteins at the molecular level, such as the fate of protein pharmaceuticals in circulation...
  79. pmc Autoimmunity to isomerized histone H2B in systemic lupus erythematosus
    Hester A Doyle
    Department of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520 8031, USA
    Autoimmunity 46:6-13. 2013
    ..Recent studies demonstrate that Asp(25) of histone H2B (H2B) spontaneously converts to an isoaspartic acid (isoAsp) in vivo...
  80. ncbi Organocatalytic synthesis of beta-alkylaspartates via beta-lactone ring opening
    Alan Armstrong
    Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom
    J Org Chem 72:8091-4. 2007
    ..Subsequent azide ring opening, reduction, and ester hydrolysis allows access to chiral beta-alkyl aspartates...
  81. ncbi Quantitating the relative abundance of isoaspartyl residues in deamidated proteins by electron capture dissociation
    Jason J Cournoyer
    Department of Chemistry, Boston University, Boston, Massachusetts, USA
    J Am Soc Mass Spectrom 18:48-56. 2007
    ..The procedure can then be used to determine the relative abundance of deamidation products from in vivo or in vitro protein aging experiments...
  82. ncbi Identification of nuclear proteins of small cell lung cancer cell line H82: An improved procedure for the analysis of silver-stained proteins
    Luis Javier Gonzalez
    Center for Genetic Engineering and Biotechnology, Havana, Cuba
    Electrophoresis 24:237-52. 2003
    ..identification of post-translational modifications, such as acetylation, phosphorylation, deamidation of asparagine residues and the presence of isoaspartic acid. A new protein variant not reported in sequence databases was also detected.
  83. ncbi Atomic resolution structure of a succinimide intermediate in E.coli CheY
    Miljan Simonovic
    Department of Biochemistry and Molecular Biology, University of Illinois College of Medicine, Chicago 60612 3796, USA
    J Mol Biol 322:663-7. 2002
    ..Stabilization of the succinimide is through interaction of a sulfate ion oxygen atom with the imide nitrogen atom. Formation of the ring caused conformational changes in the loop, but did not alter the overall structure of the protein...
  84. ncbi The presence of D-beta-aspartic acid-containing peptides in elastic fibers of sun-damaged skin: a potent marker for ultraviolet-induced skin aging
    Noriko Fujii
    Research Reactor Institute, Kyoto University Kumatori, Sennan, Osaka 590 0494, Japan
    Biochem Biophys Res Commun 294:1047-51. 2002
    ..These results suggest that UV irradiation is closely related to the formation of d-beta-Asp in the elastic fibers of skin. We propose that the antibody could be a useful indicator for sun damage of the skin...
  85. ncbi Isoaspartate in peptides and proteins: formation, significance, and analysis
    D W Aswad
    Department of Molecular Biology and Biochemistry, University of California, Irvine 92697 3900, USA
    J Pharm Biomed Anal 21:1129-36. 2000
    ..The enzyme protein L-isoaspartyl methyltransferase can be used to measure isoAsp sites in the low pmol range with or without the use of radioisotopes...
  86. ncbi Mass spectrometric differentiation of alpha- and beta-aspartic acid in a pseudo-tetrapeptide thrombosis inhibitor and its isomer
    Nganha C Luu
    Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA
    Eur J Mass Spectrom (Chichester, Eng) 10:279-87. 2004
    ..The isomers can be distinguished on the basis of this unique peak or on the basis of the different SORI energy dependence of the formation of the b(3) ions...
  87. ncbi The aspartyl replacement of the active site histidine in histidine-containing protein, HPr, of the Escherichia coli Phosphoenolpyruvate:Sugar phosphotransferase system can accept and donate a phosphoryl group. Spontaneous dephosphorylation of acyl-phospha
    S Napper
    Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada
    J Biol Chem 274:21776-82. 1999
    ..Hydrolysis of the isolated high pI form gave only aspartic acid at residue 15, and no isoaspartic acid was detected. This indicates that an isoimide rather than a succinimide is formed...
  88. pmc A second protein L-isoaspartyl methyltransferase gene in Arabidopsis produces two transcripts whose products are sequestered in the nucleus
    Qilong Xu
    Department of Horticulture, University of Kentucky Agriculture Experiment Station, S129, Agriculture Science Center North, University of Kentucky, 800 Rose Street, Lexington, KY 40546 0312, USA
    Plant Physiol 136:2652-64. 2004
    ..Furthermore, cleaved amplified polymorphic sequences from PIMT2 amplicons determined that ABA preferentially enhances the production of PIMT2omega transcript in leaves and possibly in tissues other than germinating seeds...
  89. ncbi Analysis of isoaspartate in a recombinant monoclonal antibody and its charge isoforms
    Wei Zhang
    Wyeth BioPharma, Genetics Institute Campus, One Burtt Road, Andover, MA 01810, USA
    J Pharm Biomed Anal 30:1479-90. 2003
    ..The most acidic isoforms contain approximately 0.7 mol of isoAsp per mol of protein, and no isoAsp is detected in the most basic isoform. It appears that the majority of isoAsp in the mAb is formed as a result of asparagine deamidation...
  90. ncbi Solution structure and stability of the full-length excisionase from bacteriophage HK022
    Vladimir V Rogov
    Institute of Biophysical Chemistry, J W Goethe University of Frankfurt, Germany
    Eur J Biochem 270:4846-58. 2003
    ..Such an isomerization has been previously observed and characterized only in eukaryotic proteins...
  91. ncbi Genomic organization and tissue expression of the murine gene encoding the protein beta-aspartate methyltransferase
    E A Romanik
    Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545
    Gene 118:217-22. 1992
    ..The structure and widespread expression of PCMT are characteristics of vertebrate housekeeping genes...
  92. ncbi A highly active protein repair enzyme from an extreme thermophile: the L-isoaspartyl methyltransferase from Thermotoga maritima
    J K Ichikawa
    Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, California, 90095 1569, USA
    Arch Biochem Biophys 358:222-31. 1998
    ..These data suggest that the Thermotoga enzyme has unique features for initiating repair in damaged proteins containing L-isoaspartyl residues at elevated temperatures...
  93. pmc PROTEIN L-ISOASPARTYL METHYLTRANSFERASE2 is differentially expressed in chickpea and enhances seed vigor and longevity by reducing abnormal isoaspartyl accumulation predominantly in seed nuclear proteins
    Pooja Verma
    National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi 110067, India
    Plant Physiol 161:1141-57. 2013
    ..Together, our data suggest that CaPIMT2 has most likely evolved through gene duplication, followed by subfunctionalization to specialize in repairing the nuclear proteome...
  94. pmc Considerations in the identification of endogenous substrates for protein L-isoaspartyl methyltransferase: the case of synuclein
    Gareth J Morrison
    Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, United States of America
    PLoS ONE 7:e43288. 2012
    ..The results presented here indicate that synuclein is not a major target of PIMT in vivo, and emphasize the need to minimize methyl ester hydrolysis when using methylation to assess the abundance of isoaspartyl sites in proteins...
  95. ncbi Differential contribution of isoaspartate post-translational modifications to the fibrillization and toxic properties of amyloid β and the Asn23 Iowa mutation
    Silvia Fossati
    Department of Pathology, New York University School of Medicine, New York, NY 10016, U S A
    Biochem J 456:347-60. 2013
    ..Methazolamide, a cytochrome c release inhibitor, exerted a protective effect in both cell types, suggesting that pharmacological targeting of mitochondria may constitute a viable therapeutic avenue...
  96. pmc Protein-L-isoaspartate (D-aspartate) O-methyltransferase protects cardiomyocytes against hypoxia induced apoptosis through inhibiting proapoptotic kinase Mst1
    Guijun Yan
    Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA Reproductive Medicine Center, the Affiliated Drum Tower Hospital of Nanjing University, Nanjing, China
    Int J Cardiol 168:3291-9. 2013
    ..Mst1 plays essential roles in heart disease since its activation causes cardiomyocyte apoptosis and dilated cardiomyopathy. However, the mechanism underlying Mst1 activation in the heart is not known...
  97. ncbi Accelerated aging of Asp 58 in αA crystallin and human cataract formation
    Michelle Y S Hooi
    Save Sight Institute, Sydney Eye Hospital, University of Sydney, 8 Macquarie Street, Sydney, New South Wales 2000, Australia
    Exp Eye Res 106:34-9. 2013
    ..Its more rapid formation in cataract lenses may represent an example of accelerated protein aging leading to a human age-related disease...
  98. pmc Molecular ageing of alpha- and Beta-synucleins: protein damage and repair mechanisms
    Vasanthy Vigneswara
    School of Biomedical Sciences, The University of Nottingham, Queen s Medical Centre, Nottingham, United Kingdom
    PLoS ONE 8:e61442. 2013
    ..These results provide an insight into the molecular differences between α- and β-synucleins during ageing, and highlight the susceptibility of α-synuclein to protein damage, and the potential protective role of β-synuclein...
  99. ncbi Characterization of the isomerization products of aspartate residues at two different sites in a monoclonal antibody
    Alavattam Sreedhara
    Late Stage Pharmaceutical Development, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Pharm Res 29:187-97. 2012
    ..To identify and understand isomerization products and degradation profile of different aspartate residues in an IgG1 monoclonal antibody...
  100. ncbi Assignment of the protein L-isoaspartate (D-aspartate) O-methyltransferase gene (PCMT1) to human chromosome bands 6q24-->q25 with radiation hybrid mapping
    C G DeVry
    Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095 1569, USA
    Cytogenet Cell Genet 84:130-1. 1999
  101. ncbi Regulation of enzymatic activity by deamidation and their subsequent repair by protein L-isoaspartyl methyl transferase
    Trina Dutta
    Drug Development Diagnostics, Biotechnology, Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Kolkata 700032, India
    Appl Biochem Biotechnol 168:2358-75. 2012
    ..A mass increment of the tryptic peptides of repaired enzyme due to methylation catalyzed by protein L-isoaspartyl methyl transferase substantiated the repair hypothesis...

Research Grants16

  1. The Contribution of Protein Methylation in Systemic Lupus Erythematosus
    Hester A Doyle; Fiscal Year: 2011
    ..process that occurs with lupus, protein methylation reactions, such as the conversion of aspartic acid to isoaspartic acid and arginine methylation, increase...
  2. Protein Modification: Isoaspartic Acid
    Zhaohui Sunny Zhou; Fiscal Year: 2013
    ..This project focuses on isoaspartic acid (isoAsp, isoD or beta-Asp), which is generated spontaneously from either asparagine deamidation or aspartic ..
  3. CONTROL OF EUCARYOTIC FUNCTION BY METHYLATION
    Steven Clarke; Fiscal Year: 2009
    ..abstract_text> ..
  4. Accumulation of Isoaspartyl Residue-Bearing Proteins and Alcoholic Liver Disease
    KUSUM KHARBANDA; Fiscal Year: 2009
    ....
  5. METABOLISM OF SPONTANEOUSLY DAMAGED PROTEINS IN AGING
    Stephen Young; Fiscal Year: 2002
    ..Finally, we propose to ask whether the expression of the repair methyltransferase in the extracellular compartment would limit the accumulation of spontaneous damage to extracellular proteins. ..
  6. Environmental Stresses on Protein Structure of the Repair Response in Higher Plan
    SARAH VILLA; Fiscal Year: 2007
    ..Overall, a better understanding of PIMT enzyme may lead to treatments for protein damage in humans and perhaps the partial reversal of human aging phenotypes. ..
  7. FORMATION OF ISOASPARTATE IN PEPTIDES AND PROTEINS
    DANA ASWAD; Fiscal Year: 1993
    ..These studies should provide important new information on basic mechanisms which govern the stability and integrity of proteins in vitro and in vivo...
  8. Serpin Protease Inhibitors & Opioid Neuropeptides
    Vivian Hook; Fiscal Year: 2006
    ..Serpin regulation of opioid peptides that mediate analgesia and stress may lead to development of new therapeutic approaches in pain and neurologic disease. ..
  9. INTEGRATED DNA SEQUENCING SYSTEM
    Vivian Hook; Fiscal Year: 2002
    ..abstract_text> ..
  10. FASEB Summer Research Conference-Biological Methylation
    DANA ASWAD; Fiscal Year: 2004
    ..Ample time will be provided for the 120-150 expected participants to socialize and interact on an informal basis. ..
  11. Proteomics/Genomics of Opiate Analgesia and Addiction
    Vivian Hook; Fiscal Year: 2004
    ..Elucidation of distinct pathways will be significant, since it could allow future design of opiate drug regimens that provide effective analgesia, without the tolerance and dependence of addiction. ..
  12. ENYZMES AFFECTING THE ACCUMULATION OF ALTERED PROTEINS
    Steven Clarke; Fiscal Year: 2003
    ..These studies will hopefully not only provide a new window to view protein life but may also suggest that the biological aging process may be closely linked to how well cells can keep polypeptides free of spontaneous covalent damage. ..
  13. BIOSYNTHESIS OF ENKEPHALIN OPIOID PEPTIDES
    Vivian Hook; Fiscal Year: 2009
    ..These findings will enhance our knowledge of the complexity of the endogenous opioid system. ..
  14. LENS MEMBRANE IN RELATION TO HUMAN CATARACTOGENESIS
    Larry J Takemoto; Fiscal Year: 2010
    ..Using these novel methods, we will be able to ascertain the existence of these interactions and their possible alterations during lens opacification. ..
  15. POMC Processing and Beta-Endorphine-Related Opioid Peptides
    Vivian Y H Hook; Fiscal Year: 2010
    ..New findings from this project will enhance our knowledge of the complexity of biosynthetic mechanisms for endogenous opioid and neuropeptide systems. ..
  16. Regulation of Skp2 Expression in Urinary Bladder Wall
    STEVEN WEINTRAUB; Fiscal Year: 2005
    ..These studies will be aimed at identifying targets for intervention to inhibit the hypertrophic response of the bladder wall that occurs in response to bladder outlet obstruction. ..