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Metallo-?-lactamases withstand low Zn(II) conditions by tuning metal-ligand interactions.

ABSTRACT: A number of multiresistant bacterial pathogens inactivate antibiotics by producing Zn(II)-dependent ?-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.

SUBMITTER: Gonzalez JM

PROVIDER: S-EPMC3470787 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Metallo-β-lactamases withstand low Zn(II) conditions by tuning metal-ligand interactions.

González Javier M JM Meini María-Rocío MR Tomatis Pablo E PE Medrano Martín Francisco J FJ Cricco Julia A JA Vila Alejandro J AJ

Nature chemical biology 20120624 8

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 restri ...[more]

PMID: 22729148

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