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Sci Adv. 2017 Jun 16;3(6):e1700279. doi: 10.1126/sciadv.1700279. eCollection 2017 Jun.

Splitting of the O-O bond at the heme-copper catalytic site of respiratory oxidases.

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Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.
Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland.
Department of Organic Chemistry, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.


Heme-copper oxidases catalyze the four-electron reduction of O2 to H2O at a catalytic site that is composed of a heme group, a copper ion (CuB), and a tyrosine residue. Results from earlier experimental studies have shown that the O-O bond is cleaved simultaneously with electron transfer from a low-spin heme (heme a/b), forming a ferryl state (PR ; Fe4+=O2-, CuB2+-OH-). We show that with the Thermus thermophilus ba3 oxidase, at low temperature (10°C, pH 7), electron transfer from the low-spin heme b to the catalytic site is faster by a factor of ~10 (τ ≅ 11 μs) than the formation of the PR ferryl (τ ≅110 μs), which indicates that O2 is reduced before the splitting of the O-O bond. Application of density functional theory indicates that the electron acceptor at the catalytic site is a high-energy peroxy state [Fe3+-O--O-(H+)], which is formed before the PR ferryl. The rates of heme b oxidation and PR ferryl formation were more similar at pH 10, indicating that the formation of the high-energy peroxy state involves proton transfer within the catalytic site, consistent with theory. The combined experimental and theoretical data suggest a general mechanism for O2 reduction by heme-copper oxidases.


cytochrome aa3; electron transfer; kinetics; ligand; mechanism; membrane protein; proton transfer

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