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Updated: Jul 13, 2026
08:06
The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
A minimalistic approach to identify substrate binding features in B1 Metallo-beta-lactamases
Andrés A Poeylaut-Palena1, Pablo E Tomatis, Andreas I Karsisiotis
1Instituto de Química Orgánica de Síntesis (UNR-CONICET), Suipacha 570, S2002LRK Rosario, Argentina.
Bioorganic & Medicinal Chemistry Letters
|July 24, 2007
Summary
Metallo-beta-lactamase BcII does not hydrolyze minimal beta-lactam drugs like 2-oxoazetidinylacetate sodium salt or aztreonam. Aztreonam binds nonproductively, explaining why metallo-beta-lactamases cannot inactivate monobactams.
Area of Science:
- Biochemistry
- Enzymology
- Medicinal Chemistry
Background:
- Metallo-beta-lactamases (MBLs) are a class of enzymes that hydrolyze beta-lactam antibiotics.
- Monobactams, such as aztreonam, are a class of beta-lactam antibiotics.
- Understanding MBL-monobactam interactions is crucial for developing new antibiotics.
Purpose of the Study:
- To investigate the interaction between the Metallo-beta-lactamase BcII and a minimal beta-lactam drug model.
- To determine the susceptibility of aztreonam to hydrolysis by BcII.
- To elucidate the reasons behind the resistance of monobactams to MBLs.
Main Methods:
- Synthesis of 2-oxoazetidinylacetate sodium salt as a beta-lactam model.
- Enzymatic assays using BcII with the synthesized compound and aztreonam as substrates.
- Binding studies to assess enzyme-substrate interactions.
Main Results:
- Neither 2-oxoazetidinylacetate sodium salt nor aztreonam were hydrolyzed by BcII.
- The azetidinone model compound did not bind to BcII.
- Aztreonam exhibited nonproductive binding to BcII.
Conclusions:
- Metallo-beta-lactamase BcII is unable to hydrolyze monobactams.
- Nonproductive binding of aztreonam explains its resistance to MBLs.
- Findings offer insights for designing novel MBL inhibitors.
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