Isoaspartic Acid
Aspartic Acid
Spectrometry, Mass, Electrospray Ionization
Mass Spectrometry
Systems Biology
Synthetic Biology
New Jersey
Tandem Mass Spectrometry
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Structural integrity of histone H2B in vivo requires the activity of protein L-isoaspartate O-methyltransferase, a putative protein repair enzyme. (1/34)
Protein L-isoaspartate O-methyltransferase (PIMT) is postulated to repair beta-aspartyl linkages (isoaspartyl (isoAsp)) that accumulate at certain Asp-Xaa and Asn-Xaa sites in association with protein aging and deamidation. To identify major targets of PIMT action we cultured rat PC12 cells with adenosine dialdehyde (AdOx), a methyltransferase inhibitor that promotes accumulation of isoAsp in vivo. Subcellular fractionation of AdOx-treated cells revealed marked accumulation of isoAsp in a 14-kDa nuclear protein. Gel electrophoresis and chromatography of nuclei (3)H-methylated in vitro by PIMT revealed this protein to be histone H2B. The isoAsp content of H2B in AdOx-treated cells was approximately 18 times that in control cells, although no isoAsp was seen in other core histones, regardless of treatment. To confirm the relevance and specificity of this effect, we measured isoAsp levels in histones from brains of PIMT knockout mice. IsoAsp was found at near stoichiometric levels in H2B extracted from knockout brains and was at least 80 times greater than that in H2B from normal mice. Little or no isoAsp was detected in H2A, H3, or H4 from mice of either genotype. Accumulation of isoAsp in histone H2B may disrupt normal gene regulation and contribute to the reduced life span that characterizes PIMT knockouts. In addition to disrupting protein function, isoAsp has been shown to trigger immunity against self-proteins. 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. (+info)Deamidation of asparagine in a major histocompatibility complex-bound peptide affects T cell recognition but does not explain type B reactivity. (2/34)
We have analyzed a panel of T cell hybridomas specific for the chemically dominant epitope of hen egg-white lysozyme 48-61 which has asparagine 59 as an important T cell receptor contact residue. A number of T cells recognize 48-61 with asparagine at position 59, but not the aspartic acid or isoaspartic acid derivatives. Conversely, we find T cells that specifically recognize 48-61 bearing an isoaspartic acid at residue 59, but not asparagine. For other T cells, asparagine, aspartic acid, or isoaspartic acid at residue 59 is irrelevant. We present evidence that our previous distinction between type A and type B T cells is not explained by asparagine deamidation at residue 59. (+info)Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-adenosyl homocysteine at 1.6-A resolution and modeling of an isoaspartyl-containing peptide at the active site. (3/34)
Spontaneous formation of isoaspartyl residues (isoAsp) disrupts the structure and function of many normal proteins. Protein isoaspartyl methyltransferase (PIMT) reverts many isoAsp residues to aspartate as a protein repair process. We have determined the crystal structure of human protein isoaspartyl methyltransferase (HPIMT) complexed with adenosyl homocysteine (AdoHcy) to 1.6-A resolution. The core structure has a nucleotide binding domain motif, which is structurally homologous with the N-terminal domain of the bacterial Thermotoga maritima PIMT. Highly conserved residues in PIMTs among different phyla are placed at positions critical to AdoHcy binding and orienting the isoAsp residue substrate for methylation. The AdoHcy is completely enclosed within the HPIMT and a conformational change must occur to allow exchange with adenosyl methionine (AdoMet). An ordered sequential enzyme mechanism is supported because C-terminal residues involved with AdoHcy binding also form the isoAsp peptide binding site, and a change of conformation to allow AdoHcy to escape would preclude peptide binding. Modeling experiments indicated isoAsp groups observed in some known protein crystal structures could bind to the HPIMT active site. (+info)Folate status and age affect the accumulation of L-isoaspartyl residues in rat liver proteins. (4/34)
Formation of atypical L-isoaspartyl residues in proteins and peptides is a common, spontaneous and nonenzymatic modification of aspartyl and asparaginyl sites. The enzyme protein-L-isoaspartyl methyltransferase (PIMT) catalyzes the transfer of the methyl group of S-adenosyl-L-methionine (SAM) to these L-isoaspartyl sites, thereby allowing reisomerization and restoration of the original alpha peptide linkage. Because SAM is in part a product of folate metabolism, the present study was undertaken to determine the effects of folate deficiency on the presence of L-isoaspartyl residues in hepatic proteins. Young (weanling) and older (12 mo) Sprague-Dawley rats were fed a folate-sufficient (2 mg folate/kg diet) or folate-deficient (0 mg folate/kg diet) diet for 20 wk. Liver proteins were analyzed for L-isoaspartyl residues. This analysis was based on the PIMT-dependent incorporation of [(3)H]-methyl groups from [(3)H]-SAM and the subsequent (nonenzymatic) sublimation of these methyl groups into a nonaqueous scintillant. The amount of L-isoaspartyl residues in hepatic proteins was higher in younger folate-deficient than in folate-sufficient rats (deficient: 187 +/- 71, sufficient: 64 +/- 43 pmol/mg protein, P < 0.025). This difference, however, was not seen among the older groups of rats who instead exhibited a much larger accumulation of L-isoaspartyl residues in their hepatic proteins (deficient: 528 +/- 151, sufficient: 470 +/- 204 pmol/mg protein, P = 0.568). The importance of these observations is discussed. (+info)The influence of protein structure on the products emerging from succinimide hydrolysis. (5/34)
Proteins are vulnerable to spontaneous, covalent modifications that may result in alterations to structure and function. Asparagines are particularly labile, able to undergo deamidation through the formation of a succinimide intermediate to produce either aspartate or isoaspartate residues. Although aspartates cannot undergo deamidation they can form a succinimide and result in the same products. Isoaspartyls are the principal product of succinimide hydrolysis, accounting for 65-85% of the emerging residues. The variability in the ratio of products emerging from succinimide hydrolysis suggests the ability of protein structure to influence succinimide outcome. In the H15D histidine-containing protein (HPr), phosphorylation of the active site aspartate catalyzes the formation of a cyclic intermediate. Resolution of this species is exclusively to aspartate residues, suggestive of either a succinimide with restrained hydrolysis, or an isoimide, from which aspartyl residues are the only possible product. Deletion of the C-terminal residue of this protein does not influence the ability for phosphorylation or ring formation, but it does allow for isoaspartyl formation, verifying a succinimide as the cyclic intermediate in H15D HPr. Isoaspartyl formation in H15D Delta85 is rationalized to occur as a consequence of elimination of steric restrictions imposed by the C terminus on the main-chain carbonyl of the succinimide, the required point of nucleophilic attack of a water molecule for isoaspartyl formation. This is the first reported demonstration of the influence of protein structure on the products emerging from succinimide hydrolysis. (+info)Suppression of Bcl-xL deamidation in human hepatocellular carcinomas. (6/34)
Bcl-xL is an antiapoptotic member of the Bcl-2 family, which inhibits apoptosis initiated by various cellular stresses, and has a pivotal role in the survival of tumor cells. Researchers have previously observed elevated expression of Bcl-xL in some human malignancies. In this study, we present evidence that human Bcl-xL is deamidated at asparagines 52 and 66 and that the rate of Bcl-xL deamidation is significantly lower in hepatocellular carcinomas than in normal or adjacent nontumor liver tissues. Because protein deamidation of Bcl-xL imports a complete "loss of function" of this antiapoptotic molecule, the present study indicates that tumor cells may acquire resistance to apoptosis and a survival advantage by suppressing deamidation as well as by increasing the expression of Bcl-xL. Thus, suppression of Bcl-xL deamidation may play a critical role in the regulation of cell death by apoptosis. (+info)A failure to repair self-proteins leads to T cell hyperproliferation and autoantibody production. (7/34)
It is clear that many factors can perturb T cell homeostasis that is critical in the maintenance of immune tolerance. Defects in the molecules that regulate homeostasis can lead to autoimmune pathology. This simple immunologic concept is complicated by the fact that many self-proteins undergo spontaneous posttranslational modifications that affect their biological functions. This is the case in the spontaneous conversion of aspartyl residues to isoaspartyl residues, a modification occurring at physiological pH and under conditions of cell stress and aging. We have examined the effect of isoaspartyl modifications on the effector functions of T lymphocytes in vivo using mice lacking the isoaspartyl repair enzyme protein carboxyl methyltransferase (PCMT). PCMT(-/-) CD4(+) T cells exhibit increased proliferation in response to mitogen and Ag receptor stimulation as compared with wild-type CD4(+) T cells. Hyperproliferation is marked by increased phosphorylation of members of both the TCR and CD28 signaling pathways. Wild-type mice reconstituted with PCMT(-/-) bone marrow develop high titers of anti-DNA autoantibodies and kidney pathology typical of that found in systemic lupus erythematosus. 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. (+info)Solution structure and stability of the full-length excisionase from bacteriophage HK022. (8/34)
Heteronuclear high-resolution NMR spectroscopy was employed to determine the solution structure of the excisionase protein (Xis) from the lambda-like bacteriophage HK022 and to study its sequence-specific DNA interaction. As wild-type Xis was previously characterized as a generally unstable protein, a biologically active HK022 Xis mutant with a single amino acid substitution Cys28-->Ser was used in this work. This substitution has been shown to diminish the irreversibility of Xis denaturation and subsequent degradation, but does not affect the structural or thermodynamic properties of the protein, as evidenced by NMR and differential scanning calorimetry. The solution structure of HK022 Xis forms a compact, highly ordered protein core with two well-defined alpha-helices (residues 5-11 and 18-27) and five beta-strands (residues 2-4, 30-31, 35-36, 41-44 and 48-49). These data correlate well with 1H2O-2H2O exchange experiments and imply a different organization of the HK022 Xis secondary structure elements in comparison with the previously determined structure of the bacteriophage lambda excisionase. Superposition of both Xis structures indicates a better correspondence of the full-length HK022 Xis to the typical 'winged-helix' DNA-binding motif, as found, for example, in the DNA-binding domain of the Mu-phage repressor. Residues 51-72, which were not resolved in the lambda Xis, do not show any regular structure in HK022 Xis and thus appear to be completely disordered in solution. The resonance assignments have shown, however, that an unusual connectivity exists between residues Asn66 and Gly67 owing to asparagine-isoaspartyl isomerization. Such an isomerization has been previously observed and characterized only in eukaryotic proteins. (+info)Isoaspartic acid is not typically considered a medical term, but it does have relevance to the field of medicine and biochemistry. Isoaspartic acid is a type of amino acid that can be formed as a result of a post-translational modification in proteins. Specifically, it's an isomer of aspartic acid where the peptide bond has shifted from its original position, resulting in a more reactive and unstable molecule.
In medicine, the formation of isoaspartic acid can contribute to protein misfolding and aggregation, which have been implicated in various diseases such as Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. The accumulation of damaged proteins with isoaspartic acid residues may impair cellular function and lead to tissue damage.
However, it's important to note that the presence of isoaspartic acid alone does not necessarily indicate a medical condition or disease. It can be found in various proteins under normal physiological conditions as well.
Aspartic acid is an α-amino acid with the chemical formula HO2CCH(NH2)CO2H. It is one of the twenty standard amino acids, and it is a polar, negatively charged, and hydrophilic amino acid. In proteins, aspartic acid usually occurs in its ionized form, aspartate, which has a single negative charge.
Aspartic acid plays important roles in various biological processes, including metabolism, neurotransmitter synthesis, and energy production. It is also a key component of many enzymes and proteins, where it often contributes to the formation of ionic bonds and helps stabilize protein structure.
In addition to its role as a building block of proteins, aspartic acid is also used in the synthesis of other important biological molecules, such as nucleotides, which are the building blocks of DNA and RNA. It is also a component of the dipeptide aspartame, an artificial sweetener that is widely used in food and beverages.
Like other amino acids, aspartic acid is essential for human health, but it cannot be synthesized by the body and must be obtained through the diet. Foods that are rich in aspartic acid include meat, poultry, fish, dairy products, eggs, legumes, and some fruits and vegetables.
Mass spectrometry with electrospray ionization (ESI-MS) is an analytical technique used to identify and quantify chemical species in a sample based on the mass-to-charge ratio of charged particles. In ESI-MS, analytes are ionized through the use of an electrospray, where a liquid sample is introduced through a metal capillary needle at high voltage, creating an aerosol of charged droplets. As the solvent evaporates, the analyte molecules become charged and can be directed into a mass spectrometer for analysis.
ESI-MS is particularly useful for the analysis of large biomolecules such as proteins, peptides, and nucleic acids, due to its ability to gently ionize these species without fragmentation. The technique provides information about the molecular weight and charge state of the analytes, which can be used to infer their identity and structure. Additionally, ESI-MS can be interfaced with separation techniques such as liquid chromatography (LC) for further purification and characterization of complex samples.
Mass spectrometry (MS) is an analytical technique used to identify and quantify the chemical components of a mixture or compound. It works by ionizing the sample, generating charged molecules or fragments, and then measuring their mass-to-charge ratio in a vacuum. The resulting mass spectrum provides information about the molecular weight and structure of the analytes, allowing for identification and characterization.
In simpler terms, mass spectrometry is a method used to determine what chemicals are present in a sample and in what quantities, by converting the chemicals into ions, measuring their masses, and generating a spectrum that shows the relative abundances of each ion type.
Systems Biology is a multidisciplinary approach to studying biological systems that involves the integration of various scientific disciplines such as biology, mathematics, physics, computer science, and engineering. It aims to understand how biological components, including genes, proteins, metabolites, cells, and organs, interact with each other within the context of the whole system. This approach emphasizes the emergent properties of biological systems that cannot be explained by studying individual components alone. Systems biology often involves the use of computational models to simulate and predict the behavior of complex biological systems and to design experiments for testing hypotheses about their functioning. The ultimate goal of systems biology is to develop a more comprehensive understanding of how biological systems function, with applications in fields such as medicine, agriculture, and bioengineering.
Synthetic biology is not a medical term per se, but rather it falls under the broader field of biology and bioengineering. Synthetic biology is an interdisciplinary field that combines principles from biology, engineering, chemistry, physics, and computer science to design and construct new biological parts, devices, and systems that do not exist in nature or re-design existing natural biological systems for useful purposes.
In simpler terms, synthetic biology involves the creation of artificial biological components such as genes, proteins, and cells, or the modification of existing ones to perform specific functions. These engineered biological systems can be used for a wide range of applications, including medical research, diagnostics, therapeutics, and environmental remediation.
Examples of synthetic biology in medicine include the development of synthetic gene circuits that can detect and respond to disease-causing agents or the creation of artificial cells that can produce therapeutic proteins or drugs. However, it's important to note that while synthetic biology holds great promise for improving human health, it also raises ethical, safety, and regulatory concerns that need to be carefully considered and addressed.
I'm sorry for any confusion, but "New Jersey" is not a medical term or concept. It is a state located in the Mid-Atlantic region of the United States. If you have any questions about medical terminology or concepts, I would be happy to help!
Tandem mass spectrometry (MS/MS) is a technique used to identify and quantify specific molecules, such as proteins or metabolites, within complex mixtures. This method uses two or more sequential mass analyzers to first separate ions based on their mass-to-charge ratio and then further fragment the selected ions into smaller pieces for additional analysis. The fragmentation patterns generated in MS/MS experiments can be used to determine the structure and identity of the original molecule, making it a powerful tool in various fields such as proteomics, metabolomics, and forensic science.
Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) is a type of mass spectrometry that is used to analyze large biomolecules such as proteins and peptides. In this technique, the sample is mixed with a matrix compound, which absorbs laser energy and helps to vaporize and ionize the analyte molecules.
The matrix-analyte mixture is then placed on a target plate and hit with a laser beam, causing the matrix and analyte molecules to desorb from the plate and become ionized. The ions are then accelerated through an electric field and into a mass analyzer, which separates them based on their mass-to-charge ratio.
The separated ions are then detected and recorded as a mass spectrum, which can be used to identify and quantify the analyte molecules present in the sample. MALDI-MS is particularly useful for the analysis of complex biological samples, such as tissue extracts or biological fluids, because it allows for the detection and identification of individual components within those mixtures.
Deamidation
Peptidyl-Asp metalloendopeptidase
Isoaspartate
Edman degradation
Microcystin
List of MeSH codes (D12.125)
Deamidation - Wikipedia
Antibodies | December 2023 - Browse Articles
Similar articles for PMID: 27091886 - Search Results - PubMed
Mass Spectrometry Topical Group Meetings | North Jersey Section - American Chemical Society
Plus it
Resources | MOBILion Systems
Browse by Funded research at the University of Warwick - WRAP: Warwick Research Archive Portal
Research Progress
Aspartic Acid | Profiles RNS
Pesquisa | Prevenção e Controle de Câncer
Pharmaceutical Application Standards - Standards Products - Standards & Publications - Products & Services
Quantifying Aspartic Acid Isomerization (isoAsp/isoD) - Protein Metrics
Aspartic Acid | Profiles RNS
Distinguishing d- and l-aspartic and isoaspartic acids in amyloid β peptides with ultrahigh resolution ion mobility...
MeSH Headings & Trees
ELM - Detail for LIG Integrin isoDGR 2
Project Publications: Texas A&M University: Exposure Science Core (Superfund Research Program)
Program Publications: Texas A&M University: Comprehensive Tools and Models for Addressing Exposure to Mixtures During...
MeSH Browser
MeSH Browser
Prefix: iso
DeCS
DeCS
Pesquisa | Portal Regional da BVS
Prefix: iso
NDF-RT Code NDF-RT Name
NEW (2002) MESH HEADINGS WITH SCOPE NOTES (UNIT RECORD FORMAT; 8/27/2001
Professor CHAN, Tak Wah Dominic(陳德華教授) - Department of Chemistry, The Chinese University of Hong Kong
Amino Acids3
- Deamidation is a chemical reaction in which an amide functional group in the side chain of the amino acids asparagine or glutamine is removed or converted to another functional group. (wikipedia.org)
- Amino Acids. (wikipedia.org)
- One of the non-essential amino acids commonly occurring in the L-form. (umassmed.edu)
Peptides1
- Tyler-Cross R, Schirch V (1991) Effects of amino acid sequence, buffers, and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides. (wikipedia.org)
Aspartic12
- Typically, asparagine is converted to aspartic acid or isoaspartic acid. (wikipedia.org)
- The asymmetry of the intermediate results in two products of its hydrolysis, either aspartic acid (in black at left) or isoaspartic acid, which is a beta amino acid (in green at bottom right). (wikipedia.org)
- However, there is a concern that aspartic acid can be isomerized after deamidation. (wikipedia.org)
- Asparagine Aspartic acid Peptide bond Post-translational modification Clarke, S (2003). (wikipedia.org)
- Understanding the pathway and kinetics of aspartic acid isomerization in peptide mapping methods for monoclonal antibodies. (nih.gov)
- Aspartic Acid" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)
- This graph shows the total number of publications written about "Aspartic Acid" by people in this website by year, and whether "Aspartic Acid" was a major or minor topic of these publications. (umassmed.edu)
- Below are the most recent publications written about "Aspartic Acid" by people in Profiles. (umassmed.edu)
- The mutation of aspartic acid into alanine in vitro revealed the critical role of aspartic acid 258 (corresponding to mouse amino acid site 262) of ERα for non-nuclear function. (bvsalud.org)
- Here, we studied the in vivo role of the aspartic acid 262 of ERα in the reproductive system and in the vascular tissue. (bvsalud.org)
- APPROACH AND RESULTS: We generated a mouse model harboring a point mutation of the murine counterpart of this aspartic acid into alanine (ERαD262A). (bvsalud.org)
- Isobaric Aspartic Acid (Asp, D) and iso-Aspartic Acid (isoAsp, isoD) residues are indistinguishable in MS/MS spectra using CID or HCD fragmentation, though ETD may result in signature ions z-57 and c+57, which are automatically annotated by Byonic and Byos. (proteinmetrics.com)
Specificity1
- The endoprotease, Glu-C, has shown specificity to only glutamic acid when in specific pH conditions (4.5 and 8.0) and cleaved the C-terminal side when in a solution with Tris-HCl, bicarbonate, or acetate. (wikipedia.org)
Protein1
- Asn-Gly (NG),is the most flexible and since it is acidic, it is most prone to deamidation with a half-life around 24 h under physiological conditions (pH 7.4, 37 °C). As a free amino acid, or as the N-terminal residue of a peptide or protein, glutamine deamidates readily to form pyroglutamic acid (5-oxoproline). (wikipedia.org)
Aspartic acid10
- Here, we utilized an ultrahigh resolution ion mobility spectrometry platform coupled with mass spectrometry (IMS-MS) to separate amyloid β (Aβ) peptides containing l-aspartic acid, d-aspartic acid, l-isoaspartic acid, and d-isoaspartic acid residues which span α- and β-linked amino acids in both d- and l-forms. (nih.gov)
- Typically, asparagine is converted to aspartic acid or isoaspartic acid. (wikipedia.org)
- The asymmetry of the intermediate results in two products of its hydrolysis, either aspartic acid (in black at left) or isoaspartic acid, which is a beta amino acid (in green at bottom right). (wikipedia.org)
- However, there is a concern that aspartic acid can be isomerized after deamidation. (wikipedia.org)
- Asparagine Aspartic acid Peptide bond Post-translational modification Clarke, S (2003). (wikipedia.org)
- For example "Levels of D-aspartic acid, 1-carboxyglutamic acid, polyglutamic acid, and isoaspartic acid. (nih.gov)
- 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. (nih.gov)
- It is a result of the spontaneous decomposition of aspartic acid or ASPARAGINE residues. (nih.gov)
- A PROTEIN O-METHYLTRANSFERASE that recognizes and catalyzes the methyl esterification of ISOASPARTIC ACID and D-ASPARTIC ACID residues in peptides and proteins. (bvsalud.org)
- It initiates the repair of proteins damaged by the spontaneous decomposition of normal L-aspartic acid and L-asparagine residues. (bvsalud.org)
Residues1
- Tyler-Cross R, Schirch V (1991) Effects of amino acid sequence, buffers, and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides. (wikipedia.org)
Asparagine2
- Deamidation is a chemical reaction in which an amide functional group in the side chain of the amino acids asparagine or glutamine is removed or converted to another functional group. (wikipedia.org)
- Asparagine deamidation of NGR motif yields isoDGR (isoaspartic acid-glycine-arginine) motif. (eu.org)
20241
- 2024. Kinetics of glyphosate and aminomethylphosphonic acid sorption onto montmorillonite clays in soil and their translocation to genetically modified corn. (nih.gov)
Deamidation2
- Asn-Gly (NG),is the most flexible and since it is acidic, it is most prone to deamidation with a half-life around 24 h under physiological conditions (pH 7.4, 37 °C). As a free amino acid, or as the N-terminal residue of a peptide or protein, glutamine deamidates readily to form pyroglutamic acid (5-oxoproline). (wikipedia.org)
- Deamidation proceeds much more quickly if the susceptible amino acid is followed by a small, flexible residue such as glycine whose low steric hindrance leaves the peptide group open for attack. (wikipedia.org)
Amino acid1
- The results illustrate how IMS-MS could be used to better understand age-related diseases or protein folding disorders resulting from amino acid modifications. (nih.gov)
Mobility1
- 2022. High-resolution demultiplexing (HRdm) ion mobility spectrometry-mass spectrometry for aspartic and isoaspartic acid determination and screening. (nih.gov)