title: Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases.
abstract: Haem-copper oxidase (HCO) catalyses the natural reduction of oxygen to water using a haem-copper centre. Despite decades of research on HCOs, the role of non-haem metal and the reason for nature's choice of copper over other metals such as iron remains unclear. Here, we use a biosynthetic model of HCO in myoglobin that selectively binds different non-haem metals to demonstrate 30-fold and 11-fold enhancements in the oxidase activity of Cu- and Fe-bound HCO mimics, respectively, as compared with Zn-bound mimics. Detailed electrochemical, kinetic and vibrational spectroscopic studies, in tandem with theoretical density functional theory calculations, demonstrate that the non-haem metal not only donates electrons to oxygen but also activates it for efficient O-O bond cleavage. Furthermore, the higher redox potential of copper and the enhanced weakening of the O-O bond from the higher electron density in the d orbital of copper are central to its higher oxidase activity over iron. This work resolves a long-standing question in bioenergetics, and renders a chemical-biological basis for the design of future oxygen-reduction catalysts.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Ambika
authors.initials: A
authors.lastname: Bhagi-Damodaran
authors.affiliation: Department of Biomedical Engineering, Chemistry, and Biological Sciences, Stevens Institute of Technology, Hoboken, New Jersey, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Michael
authors.affiliation: Division of Environmental &Biomolecular Systems, Institute of Environmental Health, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, USA.
authors.forename: Qianhong
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Reed
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Braddock A
authors.initials: BA
authors.lastname: Sandoval
authors.affiliation: Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Evan N
authors.initials: EN
authors.lastname: Mirts
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Saumen
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Division of Environmental &Biomolecular Systems, Institute of Environmental Health, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Moënne-Loccoz
authors.affiliation: Department of Biomedical Engineering, Chemistry, and Biological Sciences, Stevens Institute of Technology, Hoboken, New Jersey, USA.
authors.forename: Yong
authors.identifier: 0000-0001-7207-6416
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
mesh_terms: D055162:Biocatalysis; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D055664:Electrochemical Techniques; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008962:Models, Theoretical; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D015032:Zinc / Q000737:chemistry
chemical_list: D003300:Copper; D007501:Iron; D010088:Oxidoreductases; C024748:copper oxidase; D015032:Zinc; D010100:Oxygen