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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

Coordinator

UNIVERSITE DE LIEGE
Address
17,Allee De La Chimie 3 - Bètiment B6
4000 Liege
Belgium

Participants (8)

Centre National de la Recherche Scientifique (CNRS)
France
Address
17 Avenue Des Martyrs
38041 Grenoble
SAARLAND UNIVERSITY
Germany
Address
Im Stadtwald
151150 Saarbruecken
SmithKline Beecham Pharmaceuticals Ltd.
United Kingdom
Address
Third Avenue
CM19 5AD Harlow
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
South Parks Road
OX1 3QT Oxford
THE ROYAL VETERINARY AND AGRICULTURAL UNIVERSITY
Denmark
Address
40,Thorvaldsensvej 40
1871 Frederisksberg
UNIVERSIT DEGLI STUDI DI SIENA
Italy
Address
Via Bracci, 16
53100 Siena
UNIVERSITÀ DEGLI STUDI - L'AQUILA
Italy
Address
Via Vetoio
67010 Assergi
University of Leicester
United Kingdom
Address
University Road
LE1 9HN Leicester