TY - JOUR
T1 - Insights Into How Heme Reduction Potentials Modulate Enzymatic Activities of a Myoglobin-based Functional Oxidase
AU - Bhagi-Damodaran, Ambika
AU - Kahle, Maximilian
AU - Shi, Yelu
AU - Zhang, Yong
AU - Ädelroth, Pia
AU - Lu, Yi
N1 - Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - electron transfer
KW - heme proteins
KW - oxidoreductases
KW - oxygen activation
KW - redox chemistry
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U2 - 10.1002/anie.201701916
DO - 10.1002/anie.201701916
M3 - Article
C2 - 28470988
AN - SCOPUS:85018402361
SN - 1433-7851
VL - 56
SP - 6622
EP - 6626
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 23
ER -