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Conformational motions impacting function in the pancreatic-type ribonuclease superfamily

Narayanan, Chitra; Bernard, David N.; Bafna, Khusboo; Choudhary, Om P; Chennubhotla, Chakra; Agarwal, Pratul K; Doucet, Nicolas . Conformational motions impacting function in the pancreatic-type ribonuclease superfamily In: 9th Annual GRASP Symposium, 21 Novembre 2016, Université McGill, Montréal, QC.

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Résumé

Correlation between conformational dynamics and enzyme function has been well established for discrete enzyme systems, however, approaches for characterizing dynamical properties across diverse sequence homologs within a family and their correlation with enzyme activity remain challenging. Members of the pancreatic-type ribonuclease (RNase) superfamily share similarities in structure and fold, but display large variations in conformational dynamics and catalytic efficiencies, making them ideal model systems for probing the relationship between conformational motions and function. As a step towards determining the relationship between dynamics, catalytic mechanism and catalytic efficiency of various members of this broad vertebrate family, in this study, we have performed a systematic characterization of the intrinsic dynamics of over twenty RNases with experimentally solved structures over a wide range of time-scales by integrating molecular dynamics simulations and NMR 15N Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments. Our results show distinct patterns of dynamical variations between the canonical RNases clustered based on taxonomic groups. We show that conformational motions in the micro- to millisecond timescale of RNases sharing a common fold are significantly different from each other. Interestingly, sequences sharing similar conformational exchange in the catalytic timescale also share similar biological functions, suggesting that biological function, among other factors, may potentially impact dynamical properties affecting function. Further experiments are required to characterize this correlation between conserved dynamical characteristics and biological function.

Type de document: Document issu d'une conférence ou d'un atelier
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 25 juin 2018 16:31
Dernière modification: 25 juin 2018 16:31
URI: http://espace.inrs.ca/id/eprint/5809

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