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.

Dmitri and Jan to Present at XXVIth Biochemistry Congress
Poster Award for Martin
TA ČR GAMA 2 Grant for Martin
Martin to Present at XXV IUCr 2021
Open Position: Postdoc in Enzymology & Protein Engineering
Open Position: Postdoc in Protein Structural Biology
2nd Hands-on Computational Enzyme Design Course Successfully Behind Us