Carbene in Cupredoxin Protein Scaffolds: Replacement of a Histidine Ligand in the Active Site Substantially Alters Copper Redox Properties. Issue 33 (24th July 2018)

• Record Type: Journal Article
• Authors: Planchestainer, Matteo; Segaud, Nathalie; Shanmugam, Muralidharan; McMaster, Jonathan; Paradisi, Francesca; Albrecht, Martin
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 33(2018)
• Page Start: 10677
• Page End: 10682
• Publication Date: 2018-07-24
• Subjects: ligand bonding mode -- electron transfer -- histidine -- metalloenzymes -- N-heterocyclic carbenes; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201807168
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : A new view : Insertion of an N‐heterocyclic carbene ligand (green/blue) as a substitute for a His in the active site of the redox enzyme azurin reconstitutes the T1 copper center. The resulting complex is spectroscopically barely distinguishable from the N‐bonding of His or N‐methylimidazole, but substantially lowers the reduction potential of the copper center and hence facilitates electron‐transfer processes.