Dynamics and Hydration Explain Failed Functional Transformation in Dehalogenase Design

Authors

Sykora, J., Brezovsky, J., Koudelakova, T., Lahoda, M., Fortova, A., Chernovets, T., Chaloupkova, R., Stepankova, V., Prokop, Z., Kuta Smatanova, I., Hof, M., Damborsky, J.

Source

NATURE CHEMICAL BIOLOGY 10: 428-430 (2014)

Abstract

We emphasize the importance of dynamics and hydration for enzymatic catalysis and protein design by transplanting the active site from a haloalkane dehalogenase with high enantioselectivity to nonselective dehalogenase. Protein crystallography confirms that the active site geometry of the redesigned dehalogenase matches that of the target, but its enantioselectivity remains low. Time-dependent fluorescence shifts and computer simulations revealed that dynamics and hydration at the tunnel mouth differ substantially between the redesigned and target dehalogenase.

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Citation

Sykora, J., Brezovsky, J., Koudelakova, T., Lahoda, M., Fortova, A., Chernovets, T., Chaloupkova, R., Stepankova, V., Prokop, Z., Kuta Smatanova, I., Hof, M., Damborsky, J., 2014: Dynamics and Hydration Explain Failed Functional Transformation in Dehalogenase Design. Nature Chemical Biology 10: 428-430.

David, Martin and Milos to Present at ProtStab’2021
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