Titre : Conformational Diversity and Its Roal Enzyme Catalysis.
Endroit : Pavilllon J.-A.-Bombardier, salle 1035 à 11 h 30
Hôte : Professeure Joelle Pelletier

La conférence sera prononcée en anglais par le chercheur Pratuel Agarwal, Ph.D. du Oak Ridge National Laboratory au Tennessee. Elle est commanditée par l'INRS-Institut Armand-Frappier.

Résumé : Proteins are not rigid objects and they are constantly undergoing fluctuations. Evidence from an increasing number of investigations indicate that internal motions of proteins play a role in the designated function. Internal motions driven by temperature and the surrounding environment enable enzymes to sample conformational diversity formed by a hierarchy of conformational sub-states. A small number of these conformational states contain the functionally structural features for enzyme systems. The low populations in these states makes it difficult to obtain structural and dynamical information. We have developed methodology to accurately identify these states and in combination with neutron scattering and NMR investigations, computational simulations are being used to identify and more importantly quantify the populations in these functionally relevant conformational sub-states. These joint experimental-computational strategy has already provided insights into a number of enzyme systems including dihydrofolate reductase and ribonuclease A. Results from these and other enzyme systems will be presented. Overall, these hybrid methods provide a unique opportunity for investigating the conformational diversity of proteins and obtain quantitative information regarding the role of protein and solvent dynamics in enzyme catalysis.

Références :
1)  Ramanathan, A.; Savol, A.; Burger, V.; Chennubhotla, C. S.*; Agarwal, P. K.* Protein Conformational Populations and Functionally Relevant Sub-states, Accounts of Chemical Research (2014), 47(1) , 149-156.  
2) Ramanathan, A.; Savol, A.; Langmead, C. J.; Agarwal, P. K.*; Chennubhotla, C. S.* Discovering conformational sub-states relevant to protein function, PLoS ONE (2011) 6(1): e15827.
3) Ramanathan, A.; Agarwal, P. K.*Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis, PLoS Biology (2011), 9(11), e1001193.

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