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Conformational Motions Impacting Function in an Enzyme Superfamily

Narayanan, Chitra; Bernard, David N.; Bafna, Khushboo; Choudhary, Om P; Chennubhotla, Chakra; Agarwal, Pratul K et Doucet, Nicolas ORCID logoORCID: https://orcid.org/0000-0002-1952-9380 (2017). Conformational Motions Impacting Function in an Enzyme Superfamily In: Annual Meeting of the American Society for Pharmacology and Experimental Therapeutics (ASPET) at Experimental Biology Meeting, April 22-26, 2017, Chicago, Illinois.

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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 (ptRNase) superfamily share similarities in structure and fold, but display large variations in conformational dynamics, catalytic efficiencies, and tissue specific biological activities, 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 for various members of this broad vertebrate family, we have performed the 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 relaxation dispersion experiments. Our results show distinct patterns of dynamical variations between the canonical RNases clustered on taxonomic groups. We show that conformational motions on the catalytically relevant micro- to milli-second timescale are significantly different for RNases sharing a common fold. Interestingly, sequences sharing similar conformational exchange on the catalytic timescale also share similar biological functions. These results suggest that selective pressure for the conservation of specific atomic-scale dynamical behaviors, among other factors, may potentially impact distinct biological functions within the same fold. Further experiments are required to characterize this correlation between conserved dynamical properties and biological function.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Faseb Journal 31 (suppl. 1) Abstract Number:762.6
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 26 mars 2019 05:53
Dernière modification: 21 févr. 2022 20:01
URI: https://espace.inrs.ca/id/eprint/6741

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