Engineering modified ligand binding in enzymes

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The complex interplay between amino acids at the active site of enzymes results in high catalytic power and specificity. As a result of this complexity, there remains much to be done in order to extend our knowledge from specific examples to general rules. The benefits of better understanding enzyme catalysis are numerous: in our laboratory, we are gaining a better understanding of enzyme-based drug resistances and we are modifying enzymes for their application to organic synthesis. Our research program combines powerful molecular biological methodologies with computer-assisted protein molecular modelling to explore the fundamentals of enzyme catalysis. We combinatorially mutate active-site amino acids that are involved in substrate binding, creating large libraries of mutated enzymes from which we select the subset of functional ones. We characterize the new enzymes with respect to their kinetics, their structure and their dynamics to correlate active-site structure with function.