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Directed Evolution of an Artificial Imine Reductase

Hestericová, Martina and Heinisch, Tillman and Alonso-Cotchico, Lur and Maréchal, Jean-Didier and Vidossich, Pietro and Ward, Thomas R.. (2018) Directed Evolution of an Artificial Imine Reductase. Angewandte Chemie - International Edition, 57 (7). pp. 1863-1868.

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Official URL: https://edoc.unibas.ch/69106/

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Abstract

Artificial metalloenzymes, resulting from incorporation of a metal cofactor within a host protein, have received increasing attention in the last decade. The directed evolution is presented of an artificial transfer hydrogenase (ATHase) based on the biotin-streptavidin technology using a straightforward procedure allowing screening in cell-free extracts. Two streptavidin isoforms were yielded with improved catalytic activity and selectivity for the reduction of cyclic imines. The evolved ATHases were stable under biphasic catalytic conditions. The X-ray structure analysis reveals that introducing bulky residues within the active site results in flexibility changes of the cofactor, thus increasing exposure of the metal to the protein surface and leading to a reversal of enantioselectivity. This hypothesis was confirmed by a multiscale approach based mostly on molecular dynamics and protein-ligand dockings.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Bioanorganische Chemie (Ward)
UniBasel Contributors:Ward, Thomas R. R. and Ribar Hestericová, Martina and Heinisch, Tillmann
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:1433-7851
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:04 Jul 2019 11:14
Deposited On:01 Mar 2019 14:38

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