Objectif Characterization of a range of triosephophate isomerases (TIMs) which differ widely in stability. Creation of monomeric mutants of TIM by either site directed mutagenesis or complexation with tight binding cyclopeptides, or via both approaches. Eventually, with the help of model building techniques, the implementation of loop transplantations will be attempted in such a way that single monomers are formed with an altered specificity and/or new catalytic activity. The current objectives involve research on: trypanosomal TIM; human TIM; Escherichia coli TIM; octarellin design; psychrophilic TIM and thermophilic TIM; cyclopeptides; and loop transplantation modelling studies.Major results to date include: TIM variants of trypanosomal TIM and E coli TIM have been made and partly characterized;the sequences of TIM from thermophilic Bacillus Stearothermophilus and psychrotrophic Moraxella spp TA137 have been determined;the structural change from an oxopeptide to the thiopeptide cyclo(Pheomega [CSNH]-Phe-Gly-Pro-Phe-Val-) results in a drastic increase in biological activity;the crystal structure of wild type E coli TIM has been determined at 2.6 angstroms resolution.A network of European research groups has been formed to study and engineer the stability and activity of the dimeric enzyme triosephosphate isomerase (TIM) with the ultimate goal of being able to create new classes of enzymes based on the (beta alpha)8-framework. Within this collaboration psychrotrophic and thermophylic TIMs will be studied, including the crystal structure determinations. This data will help to evaluate important characteristics related to the stability of this enzyme. On the basis of the refined crystal structure of trypanosomal TIM, mutants will be made in which the dimer interface interactions are weakened. The eventual goal is to obtain monomeric TIM (complexed with or without cyclopeptides which mimic the dimer interface loops) with an altered specificity and/or new catalytic activity. Champ scientifique engineering and technologymaterials engineeringcrystalsmedical and health sciencesclinical medicinetransplantationnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP2-BRIDGE - Specific research and technological development programme (EEC) in the field of biotechnology (BRIDGE), 1990-1994 Thème(s) Data not available Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur EUROPEAN MOLECULAR BIOLOGY LABORATORY Contribution de l’UE Aucune donnée Adresse Meyerhofstrasse 1 HEIDELBERG Allemagne Voir sur la carte Coût total Aucune donnée Participants (5) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire CHRISTIAN DE DUVE INSTITUTE OF CELLULAR PATHOLOGY Belgique Contribution de l’UE Aucune donnée Adresse 74,Avenue Hippocrate 74, ICP-TROP 74.39 1200 BRUXELLES Voir sur la carte Coût total Aucune donnée Rijksuniversiteit Groningen Pays-Bas Contribution de l’UE Aucune donnée Adresse 16,Nijenborgh 9747 AG Groningen Voir sur la carte Coût total Aucune donnée Société Européenne de Biotechnologie SA Belgique Contribution de l’UE Aucune donnée Adresse 14,Rue Bois Saint-Jean 4102 Seraing Voir sur la carte Coût total Aucune donnée Technische Universität München Allemagne Contribution de l’UE Aucune donnée Adresse Lichtenbergstraße 4 85748 Garching bei München Voir sur la carte Coût total Aucune donnée Université de Liège Belgique Contribution de l’UE Aucune donnée Adresse Campus du Sart Tilman 4000 Liège Voir sur la carte Coût total Aucune donnée