A minimalistic approach to identify substrate binding features in B1 Metallo-beta-lactamases.
The 2-oxoazetidinylacetate sodium salt was synthesized as a model of a minimal beta-lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo-beta-lactamase BcII. None of them was hydrolyzed by the enzyme. While the azetidinone was not able to bind BcII, aztreonam was shown to bind in a nonproductive mode. These results provide an explanation for the unability of Metallo-beta-lactamases to inactive monobactams and give some clues for inhibitor design.
Poeylaut-Palena
Andrés A
AA
Instituto de Química Orgánica de Síntesis (UNR-CONICET), Suipacha 570, S2002LRK Rosario, Argentina.
Tomatis
Pablo E
PE
Karsisiotis
Andreas I
AI
Damblon
Christian
C
Mata
Ernesto G
EG
Vila
Alejandro J
AJ
D009682:Magnetic Resonance Spectroscopy; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000378:metabolism*
D001618:beta-Lactamases