Premium
The pH‐Induced Selectivity Between Cysteine or Histidine Coordinated Heme in an Artificial α‐Helical Metalloprotein
Author(s) -
Koebke Karl J.,
Kühl Toni,
Lojou Elisabeth,
Demeler Borries,
SchoeppCothenet Barbara,
Iranzo Olga,
Pecoraro Vincent L.,
Ivancich Anabella
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202012673
Subject(s) - heme , chemistry , histidine , hemeprotein , cofactor , metalloprotein , redox , cysteine , hemin , copper protein , stereochemistry , combinatorial chemistry , inorganic chemistry , metal , biochemistry , amino acid , organic chemistry , copper , enzyme
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 O 2 reduction when adsorbed onto a pyrolytic graphite electrode.