Welcome to the lab of Nicolas Doucet
Protein dynamics and enzyme engineering
Pasteur International Network
Summer 2016 - New Lab members
Welcome to Marie-Aude Pinoteau and Hang Pham, who just joined our lab as new PhD students!
December 2015 - Our most recent article is now published in Structure. Click here for more details.
We demonstrate how small changes in protein structure far away from the reaction site alter protein dynamics and the overall enzyme mechanism in RNase A.
April 2015 - Our research is featured on the cover of Protein Science. Click here for more details.
April 2015 - Two new articles published in Protein Science
We used the NMR chemical shift projection analysis (CHESPA) to clarify the mechanism of ligand binding in human angiogenin, further providing information on long-range intramolecular residue networks potentially involved in the function of this enzyme (see here). We also performed combinatorial active-site replacements in the BlaC β-lactamase to demonstrate that specific inhibitor-resistant (IRT) substitutions can act synergistically to yield active-site variants with several thousand fold greater in vitro resistance to clavulanate (see here).
Reportage télé : Le Code Chastenay
Ce site web servant principalement à faire connaître nos
recherches à l'extérieur des frontières du Québec, il est
rare que je prenne le temps d'écrire quelques mots en
français ici. Je fais toutefois exception pour vous
présenter un reportage télé à propos d'une (infime) partie
de nos travaux de recherche. Ce reportage de vulgarisation
scientifique, intitulé "Des arômes alimentaires
écologiques fabriqués en laboratoire", a
été diffusé sur les ondes de Télé-Québec le mardi 18 février
2014, dans le cadre de l'émission scientifique Le
Pour ceux qui seraient intéressés à visionner le reportage, vous le retrouverez en cliquant ici.
Our main research philosophy:
Can enzyme engineering benefit from the modulation of protein motions?
Doucet, N. (2011) Protein & Peptide Letters, 18(4), 336-343.
Despite impressive progress in protein engineering and design, our ability to create new and efficient enzyme activities remains a laborious and time-consuming endeavor. In the past few years, intricate combinations of rational mutagenesis, directed evolution and computational methods have paved the way to exciting engineering examples and are now offering a new perspective on the structural requirements of enzyme activity.
However, these structure-function analyses are usually guided by the time-averaged static models offered by enzyme crystals and NMR structures, which often fail to describe the functionally relevant 'invisible states' adopted by proteins in space and time. To alleviate such limitations, NMR relaxation dispersion experiments coupled to mutagenesis studies have recently been applied to the study of enzyme catalysis, effectively complementing 'structure-function' analyses with 'flexibility-function' investigations.
In addition to offering quantitative, site-specific information to help characterize residue motion, these NMR methods are now being applied to enzyme engineering purposes, providing a powerful tool to help characterize the effects of controlling long-range networks of flexible residues affecting enzyme function.