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Bioinformatique et Biologie Structurale 1 – Principes et techniques

Bioinformatique et Biologie Structurale 1 – Principes et techniques A/ L’information structurale B/ Les différentes techniques de détermination de structure C/ Les nouveaux challenges de la biologie structurale 2 – Application à l’étude d’enzymes d’intérêt médical

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Bioinformatique et Biologie Structurale 1 – Principes et techniques

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  1. Bioinformatique et Biologie Structurale 1 – Principes et techniques A/ L’information structurale B/ Les différentes techniques de détermination de structure C/Les nouveaux challenges de la biologie structurale 2 – Application à l’étude d’enzymes d’intérêt médical A/ Un bref aperçu de ce que l’on appelle « Drug design » B/ Recherche d’inhibiteurs d’aminopeptidases de Streptocoques C/ Relations structure-fonction d’hélicases impliquées dans les cancers

  2. 1 - Génomique structurale(protéomique structurale)

  3. PSI Pilot Research Centers p UK UK, Japan, Israel

  4. Ian A. Wilson, Scripps Research Institute, P50 GM062411 Technology Status – Gene to Structure CRYSTALLIZATION 2nd Generation System In use since Feb., 2001 PROTEIN PRODUCTION 4th Generation System In use since Dec, 2000 PROTEIN PURIFICATION 3rd Generation System In use since March, 2002 HT Data Collection 1st Generation System 3rd Generation Software IMAGING 1st Generation Hardware 6th Generation Software NANOVOLUME CRYSTALLIZATION Established, May 1998

  5. 504 targets in PDB (28 new folds)

  6. Structural Genomics - Public • Canada: Structural Proteomics Initiative (Ontario) • France: Structural Genomics: Pathogens (Institut Pasteur); Eukaryotes (U. Marseille); Yeast (U. PSUD) • Germany: Protein Structure Factory -- human cancer proteins (Max-Delbruck-Centrum fur MolekulareMedizin, Berlin) • Italy: Structural Genomics of Metaloproteins (U. Florence) • Japan: Structural Genomics Initiative (RIKEN) -- mouse, Arabidopsis (Protein Folds Project, Structurome Project) • UK: Functional Genomics Program (Wellcome Trust) • USA: Protein Structure Initiative (NIGMS/NIH); Structural Proteomics (DOE) • Microbacterium tuberculosis Structural Genomics Consortium [429 membres /75 institutions /15 pays] • etc… De 20 à 1500 structures résolues par centre 75000 hits dans la PDB

  7. Structural Genomics International - Industrial • Astex (Cambridge, UK) • Geneformatics (San Diego, CA) • Integrative Proteomics (Toronto, Canada) • Structural Bioinformatics (Copenhagen, Denmark) • Structure-Function Genomics (Piscataway, NJ) • Structural GenomiX, Inc. (San Diego, CA) • Structural Genomics Consortium (Wellcome Trust, pharmaceutical industry) • Syrrx (San Diego, CA)

  8. Cependant ... … les nouvelles structures ne seront pas toutes résolues automatiquement (pour l’instant, le « High throughput » ne concerne qu’1/3 des protéines clonées)

  9. 2 – Combinaison de la microscopie électronique et de la cristallographie des protéines

  10. Electron microscope / single-particle electron cryomicroscopy, or cryo-EM.

  11. Resolution 10 A

  12. The chaperonin GroEL and its cofactor GroES is the only chaperone system in E. coli that is essential under all growth conditions. http://people.cryst.bbk.ac.uk/~ubcg16z/chaperone.html

  13. 3 - Précision des données

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