Gagné, Donald; Charest, Laurie-Anne; Kovrigin, Evgenii et Doucet, Nicolas 
ORCID: 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,.
Résumé
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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