title: A functional model for the cysteinate-ligated non-heme iron enzyme superoxide reductase (SOR).
abstract: Superoxide reductases (SORs) are cysteine-ligated, non-heme iron enzymes that reduce toxic superoxide radicals (O2-). The functional role of the trans cysteinate, as well as the mechanism by which SOR reduces O2-, is unknown. Herein is described a rare example of a functional metalloenzyme analogue, which catalytically reduces superoxide in a proton-dependent mechanism, via a trans thiolate-ligated iron-peroxo intermediate, the first example of its type. Acetic-acid-promoted H2O2 release, followed by Cp2Co reduction, regenerates the active Fe(II) catalyst. The thiolate ligand and its trans positioning relative to the substrate are shown to contribute significantly to the catalyst's function, by lowering the redox potential, changing the spin state, and dramatically lowering the nuFe-O stretching frequency well-below that of any other reported iron-peroxo, while leaving nuO-O high, so as to favor superoxide reduction and Fe-O, as opposed to O-O, bond cleavage. Thus we provide critical insight into the relationship between the SOR structure and its function, as well as important benchmark parameters for characterizing highly unstable thiolate-ligated iron-peroxo intermediates.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Terutaka
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Abhishek
authors.initials: A
authors.lastname: Dey
authors.forename: Priscilla
authors.initials: P
authors.lastname: Lugo-Mas
authors.forename: Jason B
authors.initials: JB
authors.lastname: Benedict
authors.forename: Werner
authors.initials: W
authors.lastname: Kaminsky
authors.forename: Edward
authors.initials: E
authors.lastname: Solomon
authors.forename: Julie A
authors.initials: JA
authors.lastname: Kovacs
mesh_terms: D002384:Catalysis; D003545:Cysteine / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D008958:Models, Molecular; D010088:Oxidoreductases / Q000737:chemistry*; D013059:Spectrum Analysis, Raman
chemical_list: D006418:Heme; D010088:Oxidoreductases; C121849:superoxide reductase; D003545:Cysteine