Bioinformatique et Biologie Structurale 1 – Principes et techniques A/ Linformation structurale B/ Les différentes techniques de détermination de structure C/ Les nouveaux challenges de la biologie structurale 2 – Application à létude denzymes dintérêt médical A/ Un bref aperçu de ce que lon appelle « Drug design » B/ Recherche dinhibiteurs daminopeptidases de Streptocoques C/ Relations structure-fonction dhélicases impliquées dans les cancers
1 - Génomique structurale (protéomique structurale)
p PSI Pilot Research Centers UK UK, Japan, Israel
PROTEIN PRODUCTION 4 th Generation System In use since Dec, 2000 PROTEIN PURIFICATION 3 rd Generation System In use since March, 2002 CRYSTALLIZATION 2 nd Generation System In use since Feb., 2001 NANOVOLUME CRYSTALLIZATION Established, May 1998 IMAGING 1st Generation Hardware 6th Generation Software Technology Status – Gene to Structure HT Data Collection 1st Generation System 3rd Generation Software Ian A. Wilson, Scripps Research Institute, P50 GM062411
504 targets in PDB (28 new folds)
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 Molekulare Medizin, 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)
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)
Cependant... … les nouvelles structures ne seront pas toutes résolues automatiquement (pour linstant, le « High throughput » ne concerne qu1/3 des protéines clonées)
2 – Combinaison de la microscopie électronique et de la cristallographie des protéines
Electron microscope / single-particle electron cryomicroscopy, or cryo-EM.
Resolution 10 A
The chaperonin GroEL and its cofactor GroES is the only chaperone system in E. coli that is essential under all growth conditions.
3 - Précision des données