title: N-Cα Bond Cleavage of Zinc-Polyhistidine Complexes in Electron Transfer Dissociation Mediated by Zwitterion Formation: Experimental Evidence and Theoretical Analysis of the Utah-Washington Model.
abstract: Electron capture dissociation (ECD) and electron transfer dissociation (ETD) of gas-phase ions are widely used for peptide/protein sequencing by mass spectrometry. To understand the general mechanism of ECD/ETD of peptides, we focused on the ETD fragmentation of metal-peptide complexes in the absence of remote protons. Since Zn(2+) strongly binds to neutral histidine residues in peptides, Zn(2+)-polyhistidine complexation does not generate any remote protons. However, in the absence of remote protons, electron transfer to the Zn(2+)-polyhistidine complex induced the N-Cα bond cleavage. The formation pathway for the ETD products was investigated by density functional theory calculations. The calculations showed that the charge-reduced zinc-peptide radical, [M + Zn](•+), can exist in the low-energy zwitterionic amide π* states, which underwent homolytic N-Cα bond dissociation. The homolytic cleavage resulted in the donation of an electron from the N-Cα bond to the nitrogen atom, producing an iminoenol c' anion. The counterpart z(•) radical contained a radical site on the α-carbon atom. The iminoenol c' anion then abstracted a proton to presumably form the more stable amide c' fragment. The current experimental and computational joint study strongly suggested that the N-Cα bond cleavage occurred through the aminoketyl radical-anion formation for Zn(2+)-polyhistidine complexes in ETD.
authors.affiliation: National Metrology Institute of Japan (NMIJ), Research Institute for Measurement and Analytical Instrumentation, National Institute of Advanced Industrial Science and Technology (AIST) , Tsukuba Central 2, Umezono 1-1-1, Tsukuba, Ibaraki, 305-8568, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Asakawa
authors.affiliation: Department of Chemistry, Faculty of Science, Nara Women's University , Kitauoyanishi-machi, Nara, 630-8506, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Department of Chemistry, Faculty of Science, Nara Women's University , Kitauoyanishi-machi, Nara, 630-8506, Japan.
authors.forename: Shikiho
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Department of Chemistry, Faculty of Science, Nara Women's University , Kitauoyanishi-machi, Nara, 630-8506, Japan.
authors.forename: Takae
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Department of Molecular Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health , Murodo-cho 840, Izumi, Osaka, 594-1101, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Wada
mesh_terms: D002244:Carbon / Q000737:chemistry*; D004583:Electrons; D006639:Histidine / Q000737:chemistry*; D008962:Models, Theoretical; D009584:Nitrogen / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: C033223:polyhistidine; D006639:Histidine; D002244:Carbon; D015032:Zinc; D009584:Nitrogen