title: Oxidative stress-mediated N-terminal protein modifications and MS-based approaches for N-terminal proteomics.
abstract: The N-termini of peptides and proteins can be subjected to highly diverse modifications, including acetylation, myristoylation, pyroglutamylation, and epimerization. These modifications affect protein stability, localization, and activity as well as alter the chemical properties of the N-terminus. Oxidative stress is known to induce the direct oxidation of amino acid side chains and peptide backbones in proteins. Alternatively, polyunsaturated fatty acids can be oxidized to lipid hydroperoxides, which further decompose to form highly reactive aldehydes such as 4-oxo-2(E)-nonenal (ONE) and 4-hydroxy-2(E)-nonenal (HNE). ONE and HNE modify various amino acid residues and induce protein cross-linking. However, there have been few studies on oxidative stress-mediated N-terminal modifications and the resulting functional changes. Our recent studies have reported several novel N-terminal modifications that result in the formation of α-ketoamide, transamination, cyclization, and epimerization. These novel N-terminal modifications are the focus of this review. We also outline recent advances in approaches for N-terminal analysis, which have been developed over the last several decades.
authors.affiliation: Department of Bio-analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan. Electronic address: sh-lee@mail.pharm.tohoku.ac.jp.
authors.forename: Seon Hwa
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Bio-analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan. Electronic address: t-oe@mail.pharm.tohoku.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Oe
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010455:Peptides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000596:Amino Acids; D010455:Peptides; D011506:Proteins
keywords: Hydroxyl radical; Lipid hydroperoxides; Mass spectrometry; N-Terminal protein modification; N-Terminal proteomics; Oxidative stress; Reactive aldehydes