Dépôt numérique

Conservation of flexible residue clusters among structural homologues of the ribonuclease family

Gagné, Donald; Charest, Laurie-Anne; Kovrigin, Evgenii et Doucet, Nicolas ORCID logoORCID: https://orcid.org/0000-0002-1952-9380 (2012). Conservation of flexible residue clusters among structural homologues of the ribonuclease family In: 26th Annual Symposium of the Protein-Society Protein Science, May 22-25, 2011, San Diego, California,.

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Conformational flexibility between structural ensembles is an essential component of enzyme function. While the broad dynamical landscape of proteins is known to promote a number of functional events on multiple timescales, it is yet unknown whether structural and functional enzyme homologues rely on the same concerted residue motions to perform their catalytic function. It is hypothesized that networks of contiguous flexible residue motions occurring on the biologically relevant millisecond timescale evolved to promote and/ or preserve optimal enzyme catalysis. In this study, we use a combination of NMR relaxation dispersion and titration experiments to successfully capture and compare the role of conformational flexibility in two structural homologues of the pancreatic ribonuclease family: RNase A and ECP. In addition to conserving the same catalytic residues and structural fold, both homologues show similar, yet functionally distinct clusters of millisecond dynamics, suggesting that conformational flexibility can be conserved among protein folds displaying low sequence identity. The reduced conformational flexibility of ECP correlates with its lower catalytic activity, a result that can be dynamically and functionally reproduced in RNase A upon creation of a chimeric hybrid between the two proteins. These results support the hypothesis that conformational flexibility is partly required to catalytic function in homologous enzyme folds, further highlighting the importance of dynamic residue sectors in the structural organization of proteins.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique 186 Protein Science 21(suppl. 1):126
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 janv. 2024 14:59
Dernière modification: 28 janv. 2024 14:59
URI: https://espace.inrs.ca/id/eprint/14123

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