• Shuck SC, Wauchope OR, Rose KL, Kingsley PJ, Rouzer CA, Shell SM, Sugitani N, Chazin WJ, Zagol-Ikapitte I, Boutaud O, Oates JA, Galligan JJ, Beavers WN, Marnett LJ. Protein modification by adenine propenal. Chemical research in toxicology. 2014 Oct 20;27(10). 1732-42. PMID: 25211669 [PubMed]. PMCID: PMC4203390.

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. N(ε)-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 N(ε)-oxopropenyllysine. The most reactive sites for modification in human albumin are K190 and K351. Three sites of modification of XPA are in the DNA-binding domain, and two sites are subject to regulatory acetylation. Modification by adenine propenal dramatically reduces XPA's ability to bind to a DNA substrate.