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08:06
The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
Conserved water molecules stabilize the Omega-loop in class A beta-lactamases
1Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Antimicrobial Agents and Chemotherapy
|January 16, 2008
Summary
Conserved water molecules stabilize the Omega-loop in beta-lactamase enzymes. These water molecules act as structural glue, influencing enzyme evolution and structure.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Class A beta-lactamases, including TEM, SHV, and CTX-M families, are crucial in antibiotic resistance.
- The Omega-loop is a key flexible region in beta-lactamases, influencing substrate specificity and stability.
- Understanding structural stabilization mechanisms is vital for developing novel inhibitors.
Purpose of the Study:
- To investigate the role of conserved water molecules in stabilizing the Omega-loop of class A beta-lactamases.
- To analyze the structural and evolutionary implications of water molecule conservation within these enzyme families.
Main Methods:
- Systematic analysis of 49 high-resolution crystal structures (
- Identification and localization of conserved water molecules across the structural dataset.
- Correlation analysis between conserved water molecules and protein residues.
Main Results:
- 13 water molecules were conserved in at least 45 structures, with 2 conserved in all analyzed structures.
- Six conserved water molecules were identified within the Omega-loop, forming hydrogen bonds and acting as 'structural glue'.
- A correlation between conserved water and protein residues was observed specifically at the Omega-loop.
Conclusions:
- Conserved water molecules, particularly at the Omega-loop, play a significant role in stabilizing the structure of class A beta-lactamases.
- The pattern of conserved water molecules reflects the evolutionary relationships between TEM, SHV, and CTX-M families.
- These findings provide insights into enzyme structure-function relationships and potential targets for drug design.
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