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Caractérisation structurale et fonctionnelle de PBP1b de Streptococcus pneumoniae et son implication dans la découverte de nouveaux inhibiteurs

Abstract : Streptococcus pneumoniae, a major pathogen of the upper respiratory tract, is often found to be resistant to ?-lactam antibiotics, drugs which are commonly used in pneumococcal associated infections. The targets of these antibiotics are enzymes involved in bacterial peptidoglycan biosynthesis, the Penicillin-Binding Proteins (PBPs), whose active site structure is modified in resistant strains. In this work we present first the high resolution crystal structure of PBP1b, one of the three bifunctional pneumococcal PBPs, which revealed a structural reorganization of the active site as a consequence of its interaction with a pseudo-substrate of the reaction. This result led us to suggest that the active site opening plays a key role during the cell division process. Then, we solved the structures of complexes between PBP1b and various inhibitors, which can facilitate the process of rational drug-design. Finally, we characterized the glycosyltransferase domain of PBP1b, representing a new molecular target for drug development, by small angle X-ray scattering (SAXS). This original approach allowed us to provide a model concerning the organization and folding of this domain of this vital class of enzymes.
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https://tel.archives-ouvertes.fr/tel-00115254
Contributor : Pauline Macheboeuf <>
Submitted on : Monday, November 20, 2006 - 5:30:14 PM
Last modification on : Wednesday, November 4, 2020 - 1:53:24 PM
Long-term archiving on: : Tuesday, April 6, 2010 - 7:46:46 PM

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  • HAL Id : tel-00115254, version 1

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Pauline Macheboeuf. Caractérisation structurale et fonctionnelle de PBP1b de Streptococcus pneumoniae et son implication dans la découverte de nouveaux inhibiteurs. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00115254⟩

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