Bioinformatique et Biologie Structurale
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Bioinformatique et Biologie Structurale 1 – Principes et techniques PowerPoint PPT Presentation


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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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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


1 - Génomique structurale(protéomique structurale)


PSI Pilot Research Centers

p

UK

UK, Japan,

Israel


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


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 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


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 l’instant, le « High throughput » ne concerne qu’1/3 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.

http://people.cryst.bbk.ac.uk/~ubcg16z/chaperone.html


3 - Précision des données


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