Bafna, Khushboo; Narayanan, Chitra; Chennubhotla, Chakra; Doucet, Nicolas et Agarwal, Pratul K . Structurally similar human ribonucleases show divergent substrate specificity In: 2nd Protein Engineering Canada Conference (PEC), Juin 2016, Ottawa, Canada.
Ce document n'est pas hébergé sur EspaceINRS.Résumé
The enzymes of the ribonuclease (RNase) family possess identica l or similar active site residues and conserved fold architecture. The enzyme members of this fam ily preserve varying degree of ribonucleolytic activity but contribute to different biological functions. Also their catalytic efficiency of ribonucleolytic activity differ by 10 -5 –10 -6 fold. The role of structure in enzyme catalysis has been investigated for some time. However, only recently insights int o the role of internal protein motions (protein dynamics) in enzyme catalysis have become available. I t is now believed that dynamics and structure together play critical role in the function of bi omolecules including enzymes. Using theoretical modeling and atomistic molecular simulations at mic rosecond time scale, we are investigating the role of functionally important conformational sub-states in relation to optimal catalysis by the members of the pancreatic RNase enzyme family. Previous studies indicate that there is no preference for a common substrate by all members. T o obtain better insights into the mechanism of ribonucleotyic activity we have modeled 7 human RN ases and bovine RNase A each with two different model substrates (ACAC and AUAU). The r esults in ground (reactant) state indicate significant variations in the interactions of the huma n RNases family members with model substrate. For some members these model substrates remains stro ngly bound to the active-site, while for other members they are ejected within 10-20 nanosecon ds. Overall, these studies are providing us structural and dynamical insights into affinity of substrate by various members of this family.
| Type de document: | Document issu d'une conférence ou d'un atelier |
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| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 22 juin 2018 01:23 |
| Dernière modification: | 22 juin 2018 01:23 |
| URI: | https://espace.inrs.ca/id/eprint/5796 |
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