Protein modification by adenine propenal

Sarah C. Shuck, Orrette R. Wauchope, Kristie L. Rose, Philip J. Kingsley, Carol A. Rouzer, Steven M. Shell, Norie Sugitani, Walter J. Chazin, Irene Zagol-Ikapitte, Olivier Boutaud, John A. Oates, James J. Galligan, William N. Beavers, Lawrence J. Marnett

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Base propenals are products of the reaction of DNA with oxidants such as peroxynitrite and bleomycin. The most reactive base propenal, adenine propenal, is mutagenic in Escherichia coli and reacts with DNA to form covalent adducts; however, the reaction of adenine propenal with protein has not yet been investigated. A survey of the reaction of adenine propenal with amino acids revealed that lysine and cysteine form adducts, whereas histidine and arginine do not. Nε-Oxopropenyllysine, a lysine-lysine cross-link, and S-oxopropenyl cysteine are the major products. Comprehensive profiling of the reaction of adenine propenal with human serum albumin and the DNA repair protein, XPA, revealed that the only stable adduct is Nε-oxopropenyllysine. The most reactive sites for modification in human albumin are K190 and K351. Three sites of modi fication of XPA are in the DNA-binding domain, and two sites are subject to regulatory acetylation. Modi fi cation by adenine propenal dramatically reduces XPA's ability to bind to a DNA substrate. (Chemical Equation Presented).

Original languageEnglish (US)
Pages (from-to)1732-1742
Number of pages11
JournalChemical Research in Toxicology
Volume27
Issue number10
DOIs
StatePublished - Oct 20 2014
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

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