Metallo-β-lactamases Withstand Low Zn(II) Conditions by Tuning Metal-ligand Interactions

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2012 Jun 26

PMID 22729148

Citations 36

Authors

Javier M Gonzalez

Maria-Rocio Meini

Pablo E Tomatis

Francisco J Medrano Martin

Julia A Cricco

Alejandro J Vila

Affiliations

Soon will be listed here.

Abstract

A number of multiresistant bacterial pathogens inactivate antibiotics by producing Zn(II)-dependent β-lactamases. We show that metal uptake leading to an active dinuclear enzyme in the periplasmic space of Gram-negative bacteria is ensured by a cysteine residue, an unusual metal ligand in oxidizing environments. Kinetic, structural and affinity data show that such Zn(II)-cysteine interaction is an adaptive trait that tunes the metal binding affinity, thus enabling antibiotic resistance at restrictive Zn(II) concentrations.

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