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Zawartość zarchiwizowana w dniu 2024-04-30

Nmr studies of zinc b-lactamases

Cel



Research objectives and content
The most important mode of resistance to the B-lactam antibiotics occurs via their B-lactamase catalysed hydrolysis. B-actamases which require a zinc ion have received relatively little attention. Since they are resistant to inhibitors of the serine B-lactamases including clavulanic acid, the spread of zinc B-lactamase-mediated bacterial resistance to B-lactam antibiotics (including carbapenems) is frightening. In conjunction with an already existing european research project, we propose an NMR investigation of the catalytic mechanism of zinc B-lactamases. The Bacillus cereus zinc B-lactamase is expressed in E. coli and the very high yield of production allows 15N and 13C labelling of the protein. Labelled protein and its complexes with novel non-13-lactam inhibitors will be studied through Heteronuclear multidimensional NMR experiments to determine the implication of the highly conserved amino residues in the catalytic mechanism. As enzymatic activity is retained upon substitution of Zn by 1H-113Cd the role of the metal ion in the catalysis will be investigated through 1H-113Cd heteronuclear NMR.
Training content (objective, benefit and expected impact)
The success of the project will allow us to increase our knowledge of the still poorly understood catalytic mechanism of the zinc 13-lactamases, which represent a most important threat for the future of penicillin antibiotherapy.
Links with industry / industrial relevance (22)
As the design of new antibacterial compounds must rely on an improved understanding of the action of enzymes which inactivate the 13-lactam antibiotics, these studies will supply new ideas for the synthesis of potent inhibitors against the zinc 13-lactamases and new antibacterial agents.

Dziedzina nauki (EuroSciVoc)

Program(-y)

Temat(-y)

Zaproszenie do składania wniosków

Brak dostępnych danych

System finansowania

RGI - Research grants (individual fellowships)

Koordynator

University of Leicester
Wkład UE
Brak danych
Adres
University Road
LE1 9HN Leicester
Zjednoczone Królestwo
Koszt całkowity
Brak danych

Uczestnicy (1)