The project was aimed at determining the Penicillin Binding Proteins - class A (PBP) structure while co-crystallysed with the moenomycin and derivatives. Structural data of PBPs and PBPs-lead complexes would indeed allow to design a new antibiotic family: the inhibitor of the glycosyltransferase domain of PBPss.

Partnership

This project results from a partnership between Protein’eXpert and the Institute of Structural Biology. Our team closely collaborated with Dr. Otto Dideberg from the Laboratory of Macromolecular Crystallography (IBS) and Dr. Thierry Vernet from the Laboratory of Macromolecular Engineering (IBS).

Context

Streptococcus pneumoniae was recognized as a major cause of pneumonia. S. pneumoniae is the most common cause of bacterial meningitis in adults, and is one of the top two isolates found in otitis media. Pneumococcal pneumonia is more common in the immuno-compromised patients and in the younger patients.

Treatment is usually with ß-lactam antibiotics such as penicillins and cephalosporins. In the 1960s, nearly all strains of S. pneumoniae were susceptible to penicillin, but since that time, there has been an increasing prevalence of resistance, especially in areas of high antibiotic use.

Penicillin-binding proteins (PBPs) are the main targets for ß-lactam antibiotics in a wide range of bacterial species. PBP2x is a primary resistance determinant in S. pneumoniae, and its modification is an essential step in the development of high level ß-lactam resistance.

Penicillin-binding proteins solved structure

Penicillin Binding Proteins structure.

Publication

Crystal structure of the PBP2x Andréa Dessen, Nicolas Mouz, Elspeth Gordon, Julie Hopkins and Otto Dodeberg, (2001) The journal of Chemistry, 276, 45106-45112.To get further details about these publication, please click here (PDF file).