The pH-Induced Selectivity Between Cysteine or Histidine Coordinated Heme in an Artificial α-Helical Metalloprotein

Karl J. Koebke, Toni Kühl, Elisabeth Lojou, Borries Demeler, Barbara Schoepp-Cothenet, Olga Iranzo, Vincent L. Pecoraro, Anabella Ivancich

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3974-3978
Number of pages5
JournalAngewandte Chemie - International Edition
Volume60
Issue number8
DOIs
StatePublished - Feb 19 2021
Externally publishedYes

Keywords

  • EPR spectroscopy
  • cyt P450 monooxygenase
  • heme enzymes
  • protein design
  • thiolate ligands

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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