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dc.contributor.author
Rodríguez, María Margarita
dc.contributor.author
Herman, Raphaël
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Ghiglione, Barbara
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Kerff, Frédéric
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D'amico González, Gabriela Elena Noemí
dc.contributor.author
Bouillenne, Fabrice
dc.contributor.author
Galleni, Moreno
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Handelsman, Jo
dc.contributor.author
Charlier, Paulette
dc.contributor.author
Gutkind, Gabriel Osvaldo
dc.contributor.author
Sauvage, Eric
dc.contributor.author
Power, Pablo
dc.date.available
2018-12-18T16:40:10Z
dc.date.issued
2017-07
dc.identifier.citation
Rodríguez, María Margarita; Herman, Raphaël; Ghiglione, Barbara; Kerff, Frédéric; D'amico González, Gabriela Elena Noemí; et al.; Crystal structure and kinetic analysis of the class B3 di-zinc metallo-β-lactamase LRA-12 from an Alaskan soil metagenome; Public Library of Science; Plos One; 12; 7; 7-2017; 1-18
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/66662
dc.description.abstract
We analyzed the kinetic properties of the metagenomic class B3 β-lactamase LRA-12, and determined its crystallographic structure in order to compare it with prevalent metallo-β-lac-tamases (MBLs) associated with clinical pathogens. We showed that LRA-12 confers extended-spectrum resistance on E. coli when expressed from recombinant clones, and the MIC values for carbapenems were similar to those observed in enterobacteria expressing plasmid-borne MBLs such as VIM, IMP or NDM. This was in agreement with the strong carbapenemase activity displayed by LRA-12, similar to GOB β-lactamases. Among the chelating agents evaluated, dipicolinic acid inhibited the enzyme more strongly than EDTA, which required pre-incubation with the enzyme to achieve measurable inhibition. Structurally, LRA-12 contains the conserved main structural features of di-zinc class B β-lactamases, and presents unique structural signatures that differentiate this enzyme from others within the family: (i) two loops (α3-β7 and β11-α5) that could influence antibiotic entrance and remodeling of the active site cavity; (ii) a voluminous catalytic cavity probably responsible for the high hydrolytic efficiency of the enzyme; (iii) the absence of disulfide bridges; (iv) a unique Gln116 at metal-binding site 1; (v) a methionine residue at position 221that replaces Cys/Ser found in other B3 β-lactamases in a predominantly hydrophobic environment, likely playing a role in protein stability. The structure of LRA-12 indicates that MBLs exist in wild microbial populations in extreme environments, or environments with low anthropic impact, and under the appropriate antibiotic selective pressure could be captured and disseminated to pathogens.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Crystal
dc.subject
Kinetics
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Metallo-Beta-Lactamase
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Metagenome
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
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Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Crystal structure and kinetic analysis of the class B3 di-zinc metallo-β-lactamase LRA-12 from an Alaskan soil metagenome
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-11-02T17:30:21Z
dc.journal.volume
12
dc.journal.number
7
dc.journal.pagination
1-18
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Rodríguez, María Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina
dc.description.fil
Fil: Herman, Raphaël. Université de Liège; Bélgica
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Fil: Ghiglione, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina
dc.description.fil
Fil: Kerff, Frédéric. Université de Liège; Bélgica
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Fil: D'amico González, Gabriela Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina
dc.description.fil
Fil: Bouillenne, Fabrice. Université de Liège; Bélgica
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Fil: Galleni, Moreno. Université de Liège; Bélgica
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Fil: Handelsman, Jo. University of Yale; Estados Unidos
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Fil: Charlier, Paulette. Université de Liège; Bélgica
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Fil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina
dc.description.fil
Fil: Sauvage, Eric. Université de Liège; Bélgica
dc.description.fil
Fil: Power, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina
dc.journal.title
Plos One
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1371/journal.pone.0182043
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182043
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