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.

Full text •  Supplement

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.

Andrea Awarded for Excellent Research
Veronika and Jan Selected for Competitive Research Programme at Medical Faculty
New Version of CAVER PyMOL Plugin
New Website of SinFonia Project
Congratulations to Katka on her BA’s Degree
Hanka’s Success at a Student Conference
KinTek Workshop First Time in Europe