title: Protein modification by adenine propenal.
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.
authors.affiliation: A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, ‡Chemistry, and §Pharmacology, ∥Mass Spectrometry Research Center, ⊥Center in Molecular Toxicology, #Center for Structural Biology, ∇Department of Medicine, Vanderbilt Institute of Chemical Biology, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville, Tennessee 37232-0146, United States.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Shuck
authors.forename: Orrette R
authors.initials: OR
authors.lastname: Wauchope
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Rose
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kingsley
authors.forename: Carol A
authors.initials: CA
authors.lastname: Rouzer
authors.forename: Steven M
authors.initials: SM
authors.lastname: Shell
authors.forename: Norie
authors.initials: N
authors.lastname: Sugitani
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Chazin
authors.forename: Irene
authors.initials: I
authors.lastname: Zagol-Ikapitte
authors.forename: Olivier
authors.initials: O
authors.lastname: Boutaud
authors.forename: John A
authors.initials: JA
authors.lastname: Oates
authors.forename: James J
authors.initials: JJ
authors.lastname: Galligan
authors.forename: William N
authors.initials: WN
authors.lastname: Beavers
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D005454:Fluorescence Polarization; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D051760:Xeroderma Pigmentosum Group A Protein / Q000737:chemistry*
chemical_list: D010455:Peptides; D012709:Serum Albumin; D051760:Xeroderma Pigmentosum Group A Protein; C085912:9-(3-oxoprop-1-enyl)adenine; D000225:Adenine; D008239:Lysine; D003545:Cysteine