Rapid Characterization of Amyloid-  Side-Chain Oxidation by Tandem Mass Spectrometry and the Scoring Algorithm for Spectral Analysis

Schiewe, Alexandra J.; Margol, Lawrence; Soreghan, Brian A.; Thomas, Stefani N.; Yang, Austin J.

doi:10.1023/b:pham.0000032994.36343.02

Cited by 19 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most likely candidate for oxidation is the sulphur atom of methionine 35 (Met 35 ) [79,80]. Met 35 may serve as a source of electrons for the reduction of molecular oxygen to H 2 O 2 [81][82][83][84].…”

Section: Ab Redox Chemistrymentioning

confidence: 99%

Delineating the Mechanism of Alzheimer’s Disease Aβ Peptide Neurotoxicity

2007

View full text Add to dashboard Cite

The Alzheimer's disease neurotoxic amyloid-beta (A beta) peptide is derived from the larger amyloid precursor protein (APP) and is the principal component of the senile plaques in Alzheimer's disease (AD) brains. This mechanism by which A beta mediates neurotoxicity or neuronal dysfunction is not fully resolved. This review will outline some of the key determinants that modulate A beta's activity and the cellular pathways and mechanisms involved.

show abstract

Section: Ab Redox Chemistrymentioning

confidence: 99%

Delineating the Mechanism of Alzheimer’s Disease Aβ Peptide Neurotoxicity

2007

View full text Add to dashboard Cite

show abstract

“…These works reported the first evidence of a methionine transformation to a-aminobutyric acid (Abu), accompanied by the generation of thiyl radicals and subsequent isomerization of naturally occurring cis fatty acid double bonds to trans lipids. [5,6] The post-translational chemical modification of Met known to date is the corresponding sulfoxide, [7] which affects structure and function without causing peptide bond cleavage. How-A C H T U N G T R E N N U N G ever, the conversion of Met to a natural amino acid, such as Abu, can represent a variant whose biological significance is different from that arising from a genetic mutation.…”

Section: Introductionmentioning

confidence: 99%

The Reaction of Hydrogen Atoms with Methionine Residues: A Model of Reductive Radical Stress Causing Tandem Protein–Lipid Damage

et al. 2006

View full text Add to dashboard Cite

The occurrence of tandem damage, due to reductive radical stress involving proteins and lipids, is shown by using a biomimetic model. It is made of unsaturated lipid vesicle suspensions in phosphate buffer in the presence of methionine, either as a single amino acid or as part of a protein such as RNase A, which contains four methionine residues. The radical process starts with the formation of H(.) atoms by reaction of solvated electrons with dihydrogen phosphate anions, which selectively attack the thioether function of methionine. The modification of methionine to alpha-aminobutyric acid is accompanied by the formation of thiyl radicals, which in turn cause the isomerization of the cis fatty acid residues to the trans isomers. The relationship between methionine modification and lipid damage and some details of the reductive radical stress obtained by proteomic analysis of irradiated RNase A are presented.

show abstract

“…Many studies have reported that 2-oxohistidine residue had been found in various peptides and proteins (16,(43)(44)(45)(46)(47)(48)(49)(50)(51). To identify proteins which may bind specifically to 2-oxohistidine residue, we devised an experimental strategy illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of 2-oxohistidine Interacting Proteins Using E. coli Proteome Chips

Lin

Tsai

Liu

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Cellular proteins are constantly damaged by reactive oxygen species generated by cellular respiration. Because of its metal-chelating property, the histidine residue is easily oxidized in the presence of Cu/Fe ions and H 2 O 2 via metal-catalyzed oxidation, usually converted to 2-oxohistidine. We hypothesized that cells may have evolved antioxidant defenses against the generation of 2-oxohistidine residues on proteins, and therefore there would be cellular proteins which specifically interact with this oxidized side chain. Using two chemically synthesized peptide probes containing 2-oxohistidine, high-throughput interactome screening was conducted using the E. coli K12 proteome microarray containing >4200 proteins. Ten interacting proteins were identified, and successfully validated using a third peptide probe, fluorescence polarization assays, as well as binding constant measurements. We discovered that 9 out of 10 identified proteins seemed to be involved in redox-related cellular functions. We also built the functional interaction network to reveal their interacting proteins. The network showed that our interacting proteins were enriched in oxido-reduction processes, ion binding, and carbon metabolism. A consensus motif was identified among these 10 bacterial interacting proteins based on bioinformatic analysis, which also appeared to be present on human S100A1 protein. Besides, we found that the consensus binding motif among our identified proteins, including bacteria and human, were located within ␣-helices and faced the outside of proteins. The combination of chemically engineered peptide probes with proteome microarrays proves to be an efficient discovery platform for protein interactomes of unusual post-translational modifications, and sensitive enough to detect even the insertion of a single oxygen atom in this case.

show abstract

Rapid Characterization of Amyloid- Side-Chain Oxidation by Tandem Mass Spectrometry and the Scoring Algorithm for Spectral Analysis

Abstract: The combination of LC/MS/MS and SALSA searches could dramatically improve the efficiency and accuracy of determining the specific sites of oxidation of in vitro, copper-oxidized Abeta1-40 as well as other oxidized proteins.

Cited by 19 publications

References 32 publications

Delineating the Mechanism of Alzheimer’s Disease Aβ Peptide Neurotoxicity

Delineating the Mechanism of Alzheimer’s Disease Aβ Peptide Neurotoxicity

The Reaction of Hydrogen Atoms with Methionine Residues: A Model of Reductive Radical Stress Causing Tandem Protein–Lipid Damage

Identification of 2-oxohistidine Interacting Proteins Using E. coli Proteome Chips

Contact Info

Product

Resources

About