Protein Modification by Adenine Propenal

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• 作者：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
• 刊名：Chemical Research in Toxicology
• 出版年：2014
• 出版时间：October 20, 2014
• 年：2014
• 卷：27
• 期：10
• 页码：1732-1742
• 全文大小：473K
• ISSN：1520-5010

文摘

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^蔚-Oxopropenyllysine, a lysine鈥搇ysine 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^蔚-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鈥檚 ability to bind to a DNA substrate.