An artistic interpretation of the enzyme fluoroacetate dehalogenase binding substrate (green) in the left subunit and releasing bound water molecules (red) in the right-hand subunit.
The dimeric enzyme fluoroacetate dehalogenase is one of only a handful of protein catalysts that can break the strongest bond in organic chemistry, the one between carbon and fluorine atoms, in the process transforming the highly toxic pesticide fluoroacetate into glycolate, a benign molecule. The laboratories of Emil Pai and Scott Prosser, together with the group of Régis Pomès and collaborators in the US and Japan, have used a combination of X-ray crystallography, NMR and computational techniques to delineate how inter-subunit interactions in this protein contribute to enzymatic catalysis. During the whole catalytic cycle, the two chemically identical subunits never assume the same conformation. When one subunit binds the substrate molecule the second one increases its mobility and releases water molecules previously bound to the protein matrix. As these changes can revert very quickly the substrate complex is able to sample an ‘ensemble’ of conformations, some of which will be conducive to catalysis. Graduate students Pedram Mehrabi and Tae Hun Kim led the work, which addresses the question how changes in dynamics and networks of bound water molecules, i.e. entropic processes, help to accelerate reactions. The findings were published in the journal Science.
