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Conservation of Conformational Motions Impacting Function in an Enzyme Superfamily

Narayanan, Chitra; Bernard, David N.; Bafna, Khushboo; Agarwal, Pratul K; Doucet, Nicolas . Conservation of Conformational Motions Impacting Function in an Enzyme Superfamily In: 31st Annual Symposium of the Protein-Society, July 24-27, 2017, Montréal (Québec) Canada.

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Résumé

Correlation between enzyme function and conformational motions of amino acid networks>10 Å fromthe active site has been well established for discrete enzyme systems. However, approaches for charac-terizing dynamical properties across diverse sequence homologs within a family and their correlationwith enzyme activity remain challenging. Members of the pancreatic-type ribonuclease (ptRNase) super-family 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 prob-ing the relationship between conformational motions and function. As a step towards determining thisrelationship between dynamics and catalytic efficiency for various members of this broad vertebratefamily, we performed the systematic characterization of the intrinsic dynamics of>20 RNases, withexperimentally solved structures, over a wide range of time-scales by integrating molecular dynamicssimulations and NMR relaxation dispersion experiments. Our results show distinct patterns of dynamicalvariations between canonical RNases clustered into taxonomic groups, henceforth referred to as subfa-milies. We show that conformational motions on the catalytically relevant micro- to milli-second time-scale are significantly different for RNases sharing the common fold. Interestingly, sequences sharingsimilar conformational exchange on this timescale also share similar biological functions. Further, quan-titative characterization of pair-wise correlations of dynamical properties between the RNase membersshowed strong correlations within subfamilies that share similar functions. These results suggest thatselective pressure for conservation of specific atomic-scale dynamical behaviors, among other factors,may potentially impact distinct biological functions of enzymes sharing the same fold. Further experi-ments are required to characterize the correlation between conserved dynamical properties and biologi-cal function.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Protein Science (2017), 26 (suppl. 1), 77 POS194 Affiche scientifique
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 20 nov. 2019 15:41
Dernière modification: 20 nov. 2019 15:41
URI: http://espace.inrs.ca/id/eprint/8155

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