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An Artificial Hemoprotein with Inducible Peroxidase‐ and Monooxygenase‐Like Activities
Author(s) -
Kariyawasam Kalani,
Di Meo Thibault,
Hammerer Fabien,
ValerioLepiniec Marie,
Sciortino Giuseppe,
Maréchal JeanDidier,
Minard Philippe,
Mahy JeanPierre,
Urvoas Agathe,
Ricoux Rémy
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002434
Subject(s) - chemistry , monooxygenase , peroxidase , hemeprotein , circular dichroism , allosteric regulation , heme , docking (animal) , enzyme , stereochemistry , combinatorial chemistry , biochemistry , cytochrome p450 , medicine , nursing
A novel inducible artificial metalloenzyme obtained by covalent attachment of a manganese(III)‐tetraphenylporphyrin (MnTPP) to the artificial bidomain repeat protein, (A3A3′)Y26C, is reported. The protein is part of the αRep family. The biohybrid was fully characterized by MALDI‐ToF mass spectrometry, circular dichroism and UV/Vis spectroscopies. The peroxidase and monooxygenase activities were evaluated on the original and modified scaffolds including those that have a) an additional imidazole, b) a specific αRep bA3‐2 that is known to induce the opening of the (A3A3′) interdomain region and c) a derivative of the αRep bA3‐2 inducer extended with a His 6 ‐Tag (His 6 ‐bA3‐2). Catalytic profiles are highly dependent on the presence of co‐catalysts with the best activity obtained with His 6 ‐bA3‐2. The entire mechanism was rationalized by an integrative molecular modeling study that includes protein–ligand docking and large‐scale molecular dynamics. This constitutes the first example of an entirely artificial metalloenzyme with inducible peroxidase and monooxygenase activities, reminiscent of allosteric regulation of natural enzymatic pathways.