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Integrated approach to the catalytic mechanism and synthesis of inhibitors of metallo- -lactamases

Objective



Metallo-lactamases, which typically exhibit activity against a broad. Structural and mechanistic studies on enzymes are the major assets of the network and will become one of the major tools involved in the design of range of lactam antibiotics represent a new threat to oar arsenal of antimicrobial agents. The goals of the present project are to accumulate future drugs detailed knowledge on the crystal and solution structures of these enzymes intended to familiarize the young researchers with state of the art and the role of the metal ion(s) in their catalytic pathways in order to techniques in this field. giving them a deep understanding of the design and develop efficient and specific inhibitors. To attain these possibilities and limitations of each particular technique. To complete objectives, a unique integrated interdisciplinary approach will be this training, advanced courses are or will be organized by several of the teams utilized, involving, in addition to classical molecular biology and approaches followed and the problems encountered in modern drua biochemistry techniques, X-ray crystallography, Nuclear Magnetic Resonance, development mass spectrometry and spectroscopic methods dependent on the presence of metal ions in the active sites. Moreover, the role of the metal ions on the folding of the proteins and factors responsible for the stability of the only known tetrameric metallo-lactamase produced by Stenotrophomonasmaltophilia will be analysed proposal have already, thanks to a HCM Network, taken an uncontested leadership in the field. The expansion of the Network to new teams, contributing expertise in Protein NMR and Perturbed Angular Correlation Pray spectroscopy is expected to reinforce this leadership and ultimately result in the development and marketing of the designed inhibitors by an

Call for proposal

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Coordinator

UNIVERSITE DE LIEGE
EU contribution
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Address
17,Allee de la Chimie 3 - Bètiment B6
4000 LIEGE
Belgium

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Total cost
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Participants (8)