Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: González, Javier M., Meini, María-Rocío, Tomatis, Pablo E., Medrano Martín, Francisco J., Cricco, Julia A., Vila, Alejandro J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470787/
https://www.ncbi.nlm.nih.gov/pubmed/22729148
http://dx.doi.org/10.1038/nchembio.1005
Descripción
Sumario: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)-Cys interaction is an adaptive trait tuning the metal binding affinity, thus enabling antibiotic resistance at restrictive Zn(II) concentrations.