Document Detail


Aldehyde Stress-Mediated Novel Modification of Proteins: Epimerization of the N-Terminal Amino Acid.
MedLine Citation:
PMID:  24299224     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Various kinds of aldehyde-mediated chemical modifications of proteins have been identified as being exclusively covalent. We report a unique noncovalent modification: the aldehyde-mediated epimerization of the N-terminal amino acid. Epimerization of amino acids is thought to cause conformational changes that alter their biological activity. However, few mechanistic studies have been performed, because epimerization of an amino acid is a miniscule change in a whole protein. Furthermore, it does not produce a mass shift, making mass spectrometric analysis difficult. Here, we have demonstrated epimerization mediated by endogenous aldehydes. A model peptide, with an N-terminal l- or d-FMRFamide, was incubated with an endogenous or synthetic aldehyde [acetaldehyde, methylglyoxal, pyridoxal 5'-phosphate (PLP), 4-oxo-2(E)-nonenal, 4-hydroxy-2(E)-nonenal, d-glucose (Glc), 4- or 2-pyridinecarboxaldehyde] under physiological conditions. Each reaction mixture was analyzed by liquid chromatography with ultraviolet detection and/or electrospray ionization mass spectrometry. Considerable epimerization occurred after incubation with some endogenous aldehydes (PLP, 40.6% after 1 day; Glc with copper ions, 6.5% after 7 days). Moreover, the epimerization also occurred in whole proteins (human serum albumin and PLP, 26.3% after 1 day). Tandem mass spectrometric studies, including deuterium labeling and sodium borohydride reduction, suggested that the epimerization results from initial Schiff base formation followed by tautomerization to ketimine that causes the chirality to be lost. This suggests that the epimerization of the N-terminal amino acid can also occur in vivo as a post-translational modification under a high level of aldehyde stress.
Authors:
Ryo Kajita; Takaaki Goto; Seon Hwa Lee; Tomoyuki Oe
Related Documents :
22324774 - Fresh green tea and gallic acid ameliorates oxidative stress in kainic acid-induced sta...
12051774 - Acid-labile formylation of amino terminal proline of human immunodeficiency virus type ...
6790534 - Isolation and characterization of rat alpha-1-antitrypsin.
24272174 - Defensive secretion of the carabid beetlepasimachus subsulcatus.
25229854 - In vitro evaluation of glyceric acid and its glucosyl derivative, α-glucosylglyceric ac...
22610934 - An integrated process for removing the inhibitors of the pre-hydrolysis liquor of kraft...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-3
Journal Detail:
Title:  Chemical research in toxicology     Volume:  -     ISSN:  1520-5010     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University , Aobayama, Aoba-ku, Sendai 980-8578, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Safety behaviour enhances the acceptability of exposure.
Next Document:  Evaluation of a 5-day education programme in Type 1 diabetes: achieving individual targets with a pa...