PROGRAM

Wednesday 16 July 2008:(Leiden) Extra Fysisch Colloquium, Kerstin Blank (10:00 hrs)

Date:

 

Kerstin Blank Department of Chemistry, Katholieke Universiteit Leuven, Leuven (Belgium) & Laboratoire de Biologie Chimique, Institut de Science et d'Ingénierie Supramoléculaires (ISIS), Strasbourg (France)

Single Molecule Experiments for the Analysis of the Function, Regulation and Evolution of Enzymes

LION, Time 10.00 hrs, Location: De Sitterzaal - Oortgebouw

Enzymes are the catalysts of all processes of life. They are dynamic entities, which exist in a large ensemble of slightly different conformations. The equilibrium between these different conformations is defined by the underlying multidimensional energy landscape. Thermal fluctuations allow the enzyme to sample these conformations on timescales which are relevant for the catalytic reaction. As a result, the interconversion between these conformations results in observable fluctuations of the rate constants for the catalytic process.Single molecule experiments detecting the enzymatic turnover of a fluorogenic substrate into a fluorescent product give access to these rate constants. They therefore provide information about the presence of different informations and are expected to reveal how the interconversion between these different conformations is influenced by different factors such as the action of forces on the enzyme. First results show that the activity of an enzyme can be directly influenced by the application of an external force. This observation suggests that force might play an important biological role in the regulation of enzymatic activity, e.g. by stabilizing a certain conformation. This concept of stabilization or destabilization of certain conformations on the energy landscape might be a general principle in many biological processes. For example, mutations as they accumulate during evolution processes might lead to the stabilization of certain enzyme conformations thereby resulting in a higher activity or in an altered substrate specificity.

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