title: Efficient oxidation and destabilization of Zn(Cys)₄ zinc fingers by singlet oxygen.
abstract: Singlet oxygen ((1)O2) plays an important role in oxidative stress in all types of organisms, most of them being able to mount a defense against this oxidant. Recently, zinc finger proteins have been proposed to be involved in its cellular detection but the molecular basis of this process still remains unknown. We have studied the reactivity of a Zn(Cys)4 zinc finger with (1)O2 by combinations of spectroscopic and analytical techniques, focusing on the products formed and the kinetics of the reaction. We report that the cysteines of this zinc finger are oxidized to sulfinates by (1)O2. The reaction of the ZnS4 core with (1)O2 is very fast and efficient with almost no physical quenching of (1)O2. A drastic (ca. five orders of magnitude) decrease of the Zn(2+) binding constant was observed upon oxidation. This suggests that the Zn(Cys)4 zinc finger proteins would release their Zn(2+) ion and unfold upon reaction with (1)O2 under cellular conditions and that zinc finger sites are likely targets for (1)O2.
authors.affiliation: Univ. Grenoble Alpes, LCBM/PMB, and CEA, IRTSV/CBM/PMB, and CNRS, LCBM UMR 5249, PMB, 38000 Grenoble (France).
authors.forename: Vincent
authors.initials: V
authors.lastname: Lebrun
authors.forename: Arnaud
authors.initials: A
authors.lastname: Tron
authors.forename: Luca
authors.initials: L
authors.lastname: Scarpantonio
authors.forename: Colette
authors.initials: C
authors.lastname: Lebrun
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Latour
authors.forename: Nathan D
authors.initials: ND
authors.lastname: McClenaghan
authors.forename: Olivier
authors.initials: O
authors.lastname: Sénèque
mesh_terms: D003545:Cysteine / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D026082:Singlet Oxygen / Q000737:chemistry*; D013441:Sulfinic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D016335:Zinc Fingers
chemical_list: D013441:Sulfinic Acids; D026082:Singlet Oxygen; D003545:Cysteine
keywords: cysteine; metalloprotein; oxidation; singlet oxygen; sulfinic acid