Journal ArticleDOI
Racemization of individual aspartate residues in human myelin basic protein.
TLDR
Human myelin basic protein, a long‐lived brain protein, undergoes gradual racemization of its amino acids, primarily aspartic acid and serine, which is compatible with a model in which each MBP molecule interacts with adjacent cytoplasmic layers of myelin membrane through a β‐sheet on one surface and loops and helices on the other surface, thereby stabilizing the myelin multilamellar structure.Abstract:
Human myelin basic protein (MBP), a long-lived brain protein, undergoes gradual racemization of its amino acids, primarily aspartic acid and serine. Purified protein was treated at neutral pH with trypsin to yield peptides that were separated by HPLC using a C18 column. Twenty-nine peptides were isolated and analyzed for amino acid composition and aspartate racemization. Each aspartate and asparagine in the protein was racemized to a different extent, ranging from 2.2 to 17.1% D isomer. When the racemization was examined in terms of the beta-structure model of MBP, a correlation was observed in which six aspartate/asparagine residues assumed to be associated with myelin membrane lipids showed little racemization (2.2-4.9% D isomer), whereas five other aspartate residues were more highly racemized (9.9-17.1% D isomer). Although the observed aspartate racemization may be related to steric hindrance by neighboring residues and/or the protein secondary structure, interaction of aspartates with membrane lipids may also be a major factor. The data are compatible with a model in which each MBP molecule interacts with adjacent cytoplasmic layers of myelin membrane through a beta-sheet on one surface and loops and helices on the other surface, thereby stabilizing the myelin multilamellar structure.read more
Citations
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Journal ArticleDOI
Stability of Protein Pharmaceuticals: An Update
TL;DR: This review summarizes the advances that have been made since then regarding protein stabilization and formulation and discusses the current understanding of chemical and physical instability.
Journal ArticleDOI
Biological role of D-amino acid oxidase and D-aspartate oxidase. Effects of D-amino acids.
Antimo D'Aniello,Giuseppe D'Onofrio,M Pischetola,G D'Aniello,Amedeo Vetere,L Petrucelli,George H. Fisher +6 more
TL;DR: The results suggest that the in vivo biological role of these oxidases in animals is to act as detoxifying agents to metabolize D-amino acids which may have accumulated during aging.
Journal ArticleDOI
Exceptional seed longevity and robust growth: ancient Sacred Lotus from China
TL;DR: Activity of the protein-repair enzyme L-isoaspartyl methyltransferase in the old lotus seed is persistent during germination and is as robust as that in the progeny, and the degree of aspartyl racemization in proteins of the two groups of plants is minimal and essentially identical.
Journal ArticleDOI
Simultaneous racemization and isomerization at specific aspartic acid residues in alpha B-crystallin from the aged human lens.
TL;DR: It is concluded that racemization, isomerization, and oxidation of alpha B-crystallin occur spontaneously in the aging process.
Journal ArticleDOI
Isoaspartate Formation and Neurodegeneration in Alzheimer's Disease
TL;DR: PIMT is upregulated in neurodegenerative neurons and colocalizes in neurofibrillary tangles (NFTs) in AD and taken together with the enhanced protein isomerization in AD brains, it is implicated that the upregulated PIMT may associate with increased protein isomership in AD.
References
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The anatomy and taxonomy of protein structure.
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Journal ArticleDOI
Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation.
Terrence L. Geiger,Steven Clarke +1 more
TL;DR: These studies indicate that both aspartic acid and asparagine residues may be hot spots for the nonenzymatic degradation of proteins, especially in cells such as erythrocytes and eye lens, where these macromolecules must function for periods of about 120 days and 80 years, respectively.
Journal ArticleDOI
Staphylococcal Protease: A Proteolytic Enzyme Specific for Glutamoyl Bonds
Jean Houmard,Gabriel R. Drapeau +1 more
TL;DR: The staphylococcal protease hydrolyzes all of the seventeen different glutamoyl bonds studied, although those involving hydrophobic aminoacid residues with bulky side chains are cleaved at a lower rate.
Journal ArticleDOI
Aspartic acid racemisation in the human lens during ageing and in cataract formation
TL;DR: Results are reported here the results of D/L enantiomeric analyses of normal human lenses and cataracts: aspartic acid racemisation was seen during ageing andCataract formation.
Journal ArticleDOI
Aspartic acid racemisation in dentine as a measure of ageing.
TL;DR: It is shown that tooth dentine is a more suitable material, and the extent of aspartic acid racemisation in this fraction can be used as a reliable indicator of mammalian age.
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