EDC lab
We are interested in the structure and function of serine proteases, especially in the molecular determinants of substrate specificity and allosteric regulation by monovalent cations. Our main focus is on thrombin, the key enzyme of blood coagulation and the prototypic allosteric protease. Current work in the lab is aimed at unraveling the molecular determinants of thrombin allostery and the properties of the E*, E and E:Na+ forms. Emphasis is on X-ray structural studies of these forms in complex with relevant physiological substrates. We continue our systematic mutagenesis approach to validate recently identified pathways of allosteric communication involving the active site, the Na+ site and exosite I. The evolutionary origin of Na+ activation in serine proteases and its engineering in enzyme scaffolds devoid of such property remain major interests of the lab. Our experimental approaches encompass enzyme kinetics (steady state and pre-steady state), thermodynamics (calorimetry), site-directed mutagenesis, protein engineering and X-ray structural biology. Our theoretical approaches involve linkage, allostery and site-specific thermodynamics.
