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Contenido archivado el 2024-04-30

Molecular interactions of cellulases: active sites, domains and substrates

Objetivo



This project is aimed at a better understanding of the structure of cellulases and cellulosomes, the spatial relationship and interactions among the individual domains of cellulolytic systems, their multi-subunit interactions and the details of the molecular forces which govern substrate binding and catalysis. Techniques of crystallographic structure determination, molecular biology, rational design of inhibitors and substrate analogues, light, neutron and x-ray scattering, thermodynamic and kinetic studies, and molecular modeling together with electron microscopy of the enzymes and cellulosomes in interaction with crystalline cellulose will be brought together. Substantial development will be undertaken of the use of synchrotron radiation, cryocrystallographic techniques and cryo-electron microscopy.
The research results will be integrated to lay the foundations for a methodology for rational protein engineering for the production of tailor-made enzymes or multi-enzyme complexes with improved or novel catalytic activities. The controlled hydrolysis of selected regions of cellulosic fibres without adverse effects on the mechanical properties of the fibres is one of the parameters of critical interest. The project will involve three-dimensional structure determination, improvement of techniques including applications of synchrotron radiation and the development of biomolecules with desired functions thus conforming to all three aspects of the Biotechnology Work Programme - Area 6.1.
The project is highly innovative and will push the state-of-the-art well forward especially with respect to the structures of oligosaccharide complexes and the component modules of the cellulosomes, the 3-D determination of multi-subunit complexes alone or in interaction with their substrates, and the comparison of cellulases from different sources and of cellulosomes from different bacterial species. The work will also involve the design of oligosaccharide analogues for use as inhibitors, transition state mimics and for pre-steady-state kinetics. Selected catalytic subunits will be incorporated into simplified cellulosome constructs to produce tailor-made multi-enzyme complexes with novel catalytic activities.
The partnership involves leaders in their respective fields, including the laboratory of an industrial partner which currently has over 50% of the world market for cellulases and will guarantee the eventual application of the results, should they prove to have commercial value. If successful the project could lead to the much wider use of cellulases, both in current areas (e.g. textiles, detergents and the paper industry) and new fields (including paper de-inking and recycling, food and feed, and lignocellulose biomass conversion). Applications of strong and selective protein-protein and proteinpolysaccharide interactions should also be an important long term outcome. All these application areas could have important beneficial environmental consequences.

Ámbito científico (EuroSciVoc)

CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural. Véas: El vocabulario científico europeo..

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Coordinador

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Aportación de la UE
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Dirección
601,Rue de la Chimie 601, Domaine Universitaire
38041 GRENOBLE
Francia

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Participantes (6)

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