Protein Damage

Electrophiles and oxidants damage proteins by two mechanisms. First, electrophiles react to form covalent bonds with nucleophilic amino acids (e.g., cysteine thiols, lysine and histidine amines). These adducts affect the properties and functions of proteins. Second, certain electrophiles and oxidants can oxidize nucleophilic amino acid functional groups (e.g., oxidation of cysteine thiols to disulfides or methione sulfides to sulfoxides). A third type of change induced by reactive electrophiles is alteration of endogenous protein modifications that control key aspects of protein function. Modifications such as phosphorylation, acetylation, ubiquitylation and sumoylation can be perturbed by electrophiles and other types of stress. Our major research goals are to identify the targets of protein damage by reactive electrophiles and map adducts, oxidations and posttranslational modifications at the level of amino acid sequence using tandem mass spectrometry.