Publication Abstract from PubMed
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.
Dynamics and hydration explain failed functional transformation in dehalogenase design.,Sykora J, Brezovsky J, Koudelakova T, Lahoda M, Fortova A, Chernovets T, Chaloupkova R, Stepankova V, Prokop Z, Smatanova IK, Hof M, Damborsky J Nat Chem Biol. 2014 Jun;10(6):428-30. doi: 10.1038/nchembio.1502. Epub 2014 Apr, 13. PMID:24727901[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
