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Insights Into How Heme Reduction Potentials Modulate Enzymatic Activities of a Myoglobin-based Functional Oxidase |
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| Authors: | Dr Ambika Bhagi-Damodaran Maximilian Kahle Yelu Shi Prof?Dr Yong Zhang Prof?Dr Pia Ädelroth Prof?Dr Yi Lu |
| Institution: | 1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801 USA
These authors contributed equally.;2. Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-10691 Stockholm, Sweden These authors contributed equally.;3. Department of Biomedical Engineering, Chemistry and Biological Sciences, Stevens Institute of Technology, Hoboken, New Jersey, NY, 07030 USA;4. Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-10691 Stockholm, Sweden;5. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801 USA |
| Abstract: | Heme-copper oxidase (HCO) is a class of respiratory enzymes that use a heme-copper center to catalyze O2 reduction to H2O. While heme reduction potential (E°′) of different HCO types has been found to vary >500 mV, its impact on HCO activity remains poorly understood. Here, we use a set of myoglobin-based functional HCO models to investigate the mechanism by which heme E°′ modulates oxidase activity. Rapid stopped-flow kinetic measurements show that increasing heme E°′ by ca. 210 mV results in increases in electron transfer (ET) rates by 30-fold, rate of O2 binding by 12-fold, O2 dissociation by 35-fold, while decreasing O2 affinity by 3-fold. Theoretical calculations reveal that E°′ modulation has significant implications on electronic charge of both heme iron and O2, resulting in increased O2 dissociation and reduced O2 affinity at high E°′ values. Overall, this work suggests that fine-tuning E°′ in HCOs and other heme enzymes can modulate their substrate affinity, ET rate and enzymatic activity. |
| Keywords: | Elektronentransfer Hämproteine Oxidoreduktasen Redoxchemie Sauerstoffaktivierung |