BIOMAT Database Logo BIOMAT Database Logo

Protein L-isoaspartyl O-methyltransferase inhibits amyloid beta fibrillogenesis in vitro. 2011

Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
Department of Genetic Engineering, Sungkyunkwan University, Suwon, Korea.

Fibrillar aggregates of beta-amyloid peptide (Abeta) are major constituents of the senile plaques found in the brains of patients suffering from Alzheimer's disease (AD). Previous studies have shown that spontaneous isomerization or racemization of aspartyl residues in Abeta peptides leads to conformational changes in the secondary structure and increased aggregative ability of the peptides. Protein L-isoaspartyl O-methyltransferase (PIMT, EC 2.1.1.77) is a repairing enzyme converting L-isoaspartyl/D-aspartyl residues in damaged proteins to normal L-aspartyl residues. In this study it was investigated, whether PIMT is able to modulate Abeta fibrillogenesis in vitro by methylation of isoaspartyl residue using purified 5Abeta and PIMT. A Thioflavin-T (Th-T) binding assay conducted after aging Abeta in vitro (37 degrees C, pH 7.4 in PBS) revealed that PIMT inhibited the increase of fluorescence caused by amyloid fibrillogenesis. Western blot analysis revealed that high molecular Abeta aggregates (> 200 kDa) only occurred during Abeta incubation, while they were reduced in response to incubation with PIMT and AdoMet. Additionally, circular dichroism (CD) showed that the beta-sheet structure was increased in Abeta peptides in a time-dependent fashion, while PIMT suppressed the beta-sheet transition after 24 h. Finally, transmission electron microscopy (TEM) revealed that PIMT reduced the size of the Abeta aggregates and induced a different pathway, leading to the formation of amorphous structures. Taken together, these findings indicate that isoaspartyl methylation leads to partial blockade of fibrillogenesis of Abeta by inhibiting the beta transition in the Abeta peptide.

UI MeSH Term Description Entries
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D002942 Circular Dichroism A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Circular Dichroism, Vibrational,Dichroism, Circular,Vibrational Circular Dichroism
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D005456 Fluorescent Dyes Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. Flourescent Agent,Fluorescent Dye,Fluorescent Probe,Fluorescent Probes,Fluorochrome,Fluorochromes,Fluorogenic Substrates,Fluorescence Agents,Fluorescent Agents,Fluorogenic Substrate,Agents, Fluorescence,Agents, Fluorescent,Dyes, Fluorescent,Probes, Fluorescent,Substrates, Fluorogenic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013844 Thiazoles Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms. Thiazole
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein
D046529 Microscopy, Electron, Transmission Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen. Electron Diffraction Microscopy,Electron Microscopy, Transmission,Microscopy, Electron Diffraction,Transmission Electron Microscopy,Diffraction Microscopy, Electron,Microscopy, Transmission Electron

Related Publications

Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
Knock-down of protein L-isoaspartyl O-methyltransferase increases β-amyloid production by decreasing ADAM10 and ADAM17 levels.
March 2011, Acta pharmacologica Sinica,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
The protein L-isoaspartyl-O-methyltransferase functions in the Caenorhabditis elegans stress response.
December 2008, Mechanisms of ageing and development,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
Protein L-isoaspartyl methyltransferase regulates p53 activity.
June 2012, Nature communications,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
Distribution of an L-isoaspartyl protein methyltransferase in eubacteria.
January 1992, Journal of bacteriology,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
Protein l-isoAspartyl Methyltransferase (PIMT) and antioxidants in plants.
January 2023, Vitamins and hormones,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
The role of protein L-isoaspartyl/D-aspartyl O-methyltransferase (PIMT) in intracellular signal transduction.
June 2010, Chemistry & biodiversity,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity and autophagy.
March 2007, Developmental biology,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
Structure of the human gene encoding the protein repair L-isoaspartyl (D-aspartyl) O-methyltransferase.
November 1996, Archives of biochemistry and biophysics,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
Protein L-isoaspartyl methyltransferase in postmortem brains of aged humans.
January 1991, Neurobiology of aging,
Gangsoo Jung, and Jiyeon Ryu, and Jieun Heo, and Sang-Jin Lee, and Jae Youl Cho, and Sungyoul Hong
PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT) in plants: regulations and functions.
November 2020, The Biochemical journal,
Copied contents to your clipboard!