title: ROSics: chemistry and proteomics of cysteine modifications in redox biology.
abstract: Post-translational modifications (PTMs) occurring in proteins determine their functions and regulations. Proteomic tools are available to identify PTMs and have proved invaluable to expanding the inventory of these tools of nature that hold the keys to biological processes. Cysteine (Cys), the least abundant (1-2%) of amino acid residues, are unique in that they play key roles in maintaining stability of protein structure, participating in active sites of enzymes, regulating protein function and binding to metals, among others. Cys residues are major targets of reactive oxygen species (ROS), which are important mediators and modulators of various biological processes. It is therefore necessary to identify the Cys-containing ROS target proteins, as well as the sites and species of their PTMs. Cutting edge proteomic tools which have helped identify the PTMs at reactive Cys residues, have also revealed that Cys residues are modified in numerous ways. These modifications include formation of disulfide, thiosulfinate and thiosulfonate, oxidation to sulfenic, sulfinic, sulfonic acids and thiosulfonic acid, transformation to dehydroalanine (DHA) and serine, palmitoylation and farnesylation, formation of chemical adducts with glutathione, 4-hydroxynonenal and 15-deoxy PGJ2, and various other chemicals. We present here, a review of relevant ROS biology, possible chemical reactions of Cys residues and details of the proteomic strategies employed for rapid, efficient and sensitive identification of diverse and novel PTMs involving reactive Cys residues of redox-sensitive proteins. We propose a new name, "ROSics," for the science which describes the principles of mode of action of ROS at molecular levels.
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, 120-750, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sura
authors.initials: S
authors.lastname: Ha
authors.forename: Hee Yoon
authors.initials: HY
authors.lastname: Lee
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000378:metabolism; D000447:Aldehydes / Q000737:chemistry; D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D054878:Lipoylation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D054876:Prenylation; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species / Q000737:chemistry*; D012694:Serine / Q000378:metabolism; D013441:Sulfinic Acids / Q000737:chemistry; D013886:Thiosulfonic Acids / Q000737:chemistry
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000447:Aldehydes; D004220:Disulfides; D017382:Reactive Oxygen Species; D013441:Sulfinic Acids; D013886:Thiosulfonic Acids; C100040:thiosulfinic acids; D012694:Serine; C015102:dehydroalanine; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D003545:Cysteine; D000409:Alanine; D015230:Prostaglandin D2
keywords: ROSics; cysteine modification; cysteine reactivity; dehydroalanine; disulfide; mass spectrometry; proteomics; reactive oxygen species (ROS); redox biology; thiosulfonic acid