Cofactor Binding Dynamics Influence the Catalytic Activity and Selectivity of an Artificial Metalloenzyme
Villarino, Lara (University of Groningen)
Chordia, Shreyans (University of Groningen)
Alonso-Cotchico, Lur (University of Groningen)
Reddem, Eswar (University of Groningen)
Zhou, Zhi (University of Groningen)
Thunnissen, Andy Mark W. H. (University of Groningen)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)
Roelfes, Gerard (University of Groningen)

Data:	2020
Resum:	We present an artificial metalloenzyme based on the transcriptional regulator LmrR that exhibits dynamics involving the positioning of its abiological metal cofactor. The position of the cofactor, in turn, was found to be related to the preferred catalytic reactivity, which is either the enantioselective Friedel-Crafts alkylation of indoles with β-substituted enones or the tandem Friedel-Crafts alkylation/enantioselective protonation of indoles with α-substituted enones. The artificial metalloenzyme could be specialized for one of these catalytic reactions introducing a single mutation in the protein. The relation between cofactor dynamics and activity and selectivity in catalysis has not been described for natural enzymes and, to date, appears to be particular for artificial metalloenzymes.
Ajuts:	European Commission 280010 Agencia Estatal de Investigación CTQ2017-87889-P
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Artificial metalloenzymes ; Biocatalysis ; Structural dynamics ; Enzyme design ; Copper
Publicat a:	ACS catalysis, Vol. 10, Num 20 (2020) , p. 11783-11790, ISSN 2155-5435

DOI: 10.1021/acscatal.0c01619
PMID: 33101759

8 p, 4.1 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats