The pH-induced selectivity between cysteine or histidine coordinated heme in an artificial α-helical metalloprotein
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Date
2021
Authors
Koebke, Karl J.
Kühl, Toni
Lojou, Elisabeth
Demeler, Borries
Schoepp-Cothenet, Barbara
Iranzo, Olga
Pecoraro, Vincent L.
Ivancich, Anabella
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
De Novo metalloprotein design assesses the relationship between metal active site architecture and catalytic reactivity. Herein, we use an α-helical scaffold to control the iron coordination geometry when a heme cofactor is allowed to bind to either histidine or cysteine ligands, within a single artificial protein. Consequently, we uncovered a reversible pH-induced switch of the heme axial ligation within this simplified scaffold. Characterization of the specific heme coordination modes was done by using UV-Vis and Electron Paramagnetic Resonance spectroscopies. The penta- or hexa-coordinate thiolate heme (9 ≤ pH ≤ 11) and the penta-coordinate imidazole heme (6 ≤ pH ≤ 8.5) reproduces well the heme ligation in chloroperoxidases or cyt P450 monooxygenases and peroxidases, respectively. The stability of heme coordination upon ferric/ferrous redox cycling is a crucial property of the construct. At basic pHs, the thiolate mini-heme protein can catalyze O2 reduction when adsorbed onto a pyrolytic graphite electrode.
Description
Accepted author manuscript
Keywords
De Novo protein design , Cyt P450 monooxygenase , Heme enzymes , Thiolate ligands , EPR spectroscopy
Citation
Koebke, K. J., Kühl, T., Lojou, E., Demeler, B., Schoepp-Cothenet, B., Iranzo, O., Pecoraro, V. L., & Ivancich, A. (2021). The pH-induced selectivity between cysteine or histidine coordinated heme in an artificial α-helical metalloprotein. Angewandte Chemie International Edition, 2021, 60(8), 3974-3978. https://doi.org/10.1002/anie.202012673