Dynamics and hydration explain failed functional transformation in dehalogenase design

April 13th, 2014 by Jan Sykora

Nature Chemical Biology 10, 428 (2014). doi:10.1038/nchembio.1502

Authors: Jan Sykora, Jan Brezovsky, Tana Koudelakova, Maryna Lahoda, Andrea Fortova, Tatsiana Chernovets, Radka Chaloupkova, Veronika Stepankova, Zbynek Prokop, Ivana Kuta Smatanova, Martin Hof & Jiri Damborsky

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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