Dynamics of Metal Complex Binding in Relation to Catalytic Activity and Selectivity of an Artificial Metalloenzyme

Lara Villarino, Shreyans Chordia, Lur Alonso-Cotchico, Eswar R. Reddem, Andy-Mark Thunnissen, Jean-Didier Maréchal, Gerard Roelfes

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Resum

Structural dynamics is important in enzymes to achieve optimal complementarity to the activated complex
of the catalyzed reaction and, hence, give rise to rate acceleration and (enantio)selectivity. Here, we present
an artificial metalloenzyme based on the transcriptional regulator LmrR that exhibits a unique form of
structural 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 by introducing a single mutation in the protein. The switching
of catalytic activity by dynamic interconversion of the position of a metal cofactor has not been described for
natural enzymes and, to date, appears to be unique to supramolecularly assembled artificial metalloenzymes.
Idioma originalEnglish
Nombre de pàgines14
DOIs
Estat de la publicacióPublicada - 12 de març 2020

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