title: Pro-oxidant activity of histatin 5 related Cu(II)-model peptide probed by mass spectrometry.
abstract: Histatin 5 is a cationic salivary peptide with strong candidacidal and bactericidal activity at physiological concentration. In this paper we demonstrate by optical spectroscopy and ESI-IT-MS experiments that a synthetic peptide related to the N-terminus of histatin 5 specifically binds copper ions in vitro and that the complex metal-peptide generates reactive oxygen species at physiological concentration of ascorbate, leading to significant auto-oxidation of the peptide within short reaction time. The oxidative activity of this peptide is associated to the presence of a specific metal binding site present at its N-terminus. The motif is constituted by the amino acid sequence NH(2)-Asp-Ser-His, representing a copper and nickel amino terminal binding site, known as "ATCUN motif". The results of the study suggest that the production of reactive oxygen species can be an intrinsic property of histatin 5 connected to its ability to bind metals.
authors.affiliation: Dipartimento di Scienze Applicate ai Biosistemi, Università di Cagliari, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cabras
authors.forename: Maria
authors.initials: M
authors.lastname: Patamia
authors.forename: Sonia
authors.initials: S
authors.lastname: Melino
authors.forename: Rosanna
authors.initials: R
authors.lastname: Inzitari
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnola
authors.forename: Raffaele
authors.initials: R
authors.lastname: Petruzzelli
mesh_terms: D020816:Amino Acid Motifs; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D054808:Histatins; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000737:chemistry; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D023181:Antimicrobial Cationic Peptides; C068075:HTN3 protein, human; D054808:Histatins; D009842:Oligopeptides; D017382:Reactive Oxygen Species; D012471:Salivary Proteins and Peptides; D003300:Copper