Insights Into How Heme Reduction Potentials Modulate Enzymatic Activities of a Myoglobin-based Functional Oxidase

Angewandte Chemie - International Edition

5 years ago

Insights Into How Heme Reduction Potentials Modulate Enzymatic Activities of a Myoglobin-based Functional Oxidase

Yong Zhang, Yelu Shi, Pia Ädelroth, Maximilian Kahle, Ambika Bhagi-Damodaran, Yi Lu

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. A four-electron reduction of O2 to H2O in heme-copper oxidase (HCO) requires an efficient control of electron transfer, O2 binding/dissociation rates and O2 affinity. By employing a functional model of HCO, it is shown that the heme reduction potential plays a key role in controlling these parameters, the electronics of bound O2, and thus the overall enzymatic activity.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201701916