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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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slide1

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

slide5

PSI Pilot Research Centers

p

UK

UK, Japan,

Israel

slide6

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

structural genomics public
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
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)
slide15

Cependant ...

… les nouvelles structures ne seront pas toutes résolues automatiquement

(pour l’instant, le « High throughput » ne concerne qu’1/3 des protéines clonées)

slide19

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

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