Tuning Zinc Affinity Against ß-Lactams

Tuning Zinc Affinity Against ß-Lactams

Author: Melania Tesio

ß-lactams, a family of antibiotics whose activity depends on a ß-lactam ring (pictured), fight a wide spectrum of bacterial infections. Nevertheless, their therapeutic properties are hampered by ß-lactamases, bacterial hydrolases that inactivate the β-lactam ring and confer antibiotic resistance.

Javier González, Universidad Nacional de Rosario, Argentina, and colleagues have demonstrated that B1 Zn(II)-dependent ß-lactamases are crucially regulated by cysteine-Zn(II) interactions.
The in vivo activity of the enzyme is determined by Zn(II) availability. The presence of a cysteine residue in position 221 is essential to tune zinc binding affinity, guaranteeing an optimal metal uptake and, thus, the catalysis even at limiting metal concentrations.

By providing a new structural understanding of ß-lactamases’ activity, this study opens the doors for generating metallo ß-lactamase inhibitors targeting resistant bacteria.

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