KE07-LDH

Application of directed evolution to the study of structural enzyme dynamics

Coordinatore	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE    more  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Dr. Nome: Jean-Xavier Cognome: Boucherle Email: send email Telefono: -76887895 Fax: -76881145
Nazionalità Coordinatore	France [FR]
Totale costo	0 €
EC contributo	167˙145 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-IIF-2008
Funding Scheme	MC-IIF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-06-01   -   2011-05-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Dr. Nome: Jean-Xavier Cognome: Boucherle Email: send email Telefono: -76887895 Fax: -76881145	FR (PARIS)	coordinator	167˙145.56

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 Obiettivo del progetto (Objective)

'We propose to study the importance of structural dynamics to enzymatic catalysis. This will utilise simplified model systems in which a variety of catalytically distinct mutants have been generated though directed evolution. This research will focus on whether changes to the conformational landscape of enzymes affect catalysis and how the structural scaffold can determine the optimum temperature for enzymatic activity. Two model systems will be used: (i) the lactate dehydrogenase family, chosen because it is the most heavily studied family with regards to thermophilicity; (ii) a designed Kemp elimination catalyst, chosen because it is the first example of an enzyme in which the evolution of the active site and structural scaffold has been decoupled. A synergistic experimental approach will be used to study the mutants generated through directed evolution: - Biophysics (temperature-controlled cryo-crystallography, incoherent neutron scattering, in-cristallo spectroscopy) and detailed data analysis (anisotropic and multiple crystallographic refinement) - Enzyme kinetics (temperature dependent kinetics and Arrhenius plots) - Computational simulation (normal mode analysis and molecular dynamics) This project will constitute, to our knowledge, one of the first attempts to apply directed evolution to the systematic analysis of the importance and evolution of pathways for dynamic conformational change in enzymatic catalysis.'