Carbene in Cupredoxin Protein Scaffolds: Replacement of a Histidine Ligand in the Active Site Substantially Alters Copper Redox Properties

Planchestainer, Matteo; Segaud, Nathalie; Shanmugam, Muralidharan; McMaster, Jonathan; Paradisi, Francesca; Albrecht, Martin

Abstract

N‐heterocyclic carbene (NHC) ligands have had a major impact in homogeneous catalysis, however, their potential role in biological systems is essentially unexplored. We replaced a copper‐coordinating histidine (His) in the active site of the redox enzyme azurin with exogenous dimethyl imidazolylidene. This NHC rapidly restores the type‐1 Cu center, with spectroscopic properties (EPR, UV/Vis) that are identical to those from N‐coordination of the His in the wild type. However, the introduction of the NHC markedly alters the redox potential of the metal, which is a key functionality of this blue copper protein. These results suggest that C‐bonding for histidine is plausible and a potentially relevant bonding mode of redox‐active metalloenzymes in their (transient) active states.

Citation

Planchestainer, M., Segaud, N., Shanmugam, M., McMaster, J., Paradisi, F., & Albrecht, M. (2018). Carbene in Cupredoxin Protein Scaffolds: Replacement of a Histidine Ligand in the Active Site Substantially Alters Copper Redox Properties. Angewandte Chemie, 130(33), 10837-10842. https://doi.org/10.1002/ange.201807168

• Journal Article Type: Article
• Acceptance Date: Jun 27, 2018
• Online Publication Date: Jun 27, 2018
• Publication Date: Aug 13, 2018
• Deposit Date: Apr 1, 2021
• Journal: Angewandte Chemie
• Print ISSN: 0044-8249
• Electronic ISSN: 1521-3757
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 130
• Issue: 33
• Pages: 10837-10842
• DOI: https://doi.org/10.1002/ange.201807168
• Keywords: General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4928665
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1002/ange.201807168
• Additional Information: Received: 2018-06-21; Published: 2018-07-24