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dc.contributor.author
Fishovitz, Jennifer
dc.contributor.author
Rojas Altuve, Alzoray
dc.contributor.author
Otero, Lisandro Horacio
dc.contributor.author
Dawley, Matthew
dc.contributor.author
Carrasco López, Cesar
dc.contributor.author
Chang, Mayland
dc.contributor.author
Hermoso, Juan Antonio
dc.contributor.author
Mobashery, Shahriar
dc.date.available
2016-11-24T15:25:52Z
dc.date.issued
2014
dc.identifier.citation
Fishovitz, Jennifer; Rojas Altuve, Alzoray; Otero, Lisandro Horacio; Dawley, Matthew; Carrasco López, Cesar; et al.; Disruption of Allosteric Response as an Unprecedented Mechanism of Resistance to Antibiotics; American Chemical Society; Journal Of The American Chemical Society; 136; 28; -1-2014; 9814-9817
dc.identifier.issn
0002-7863
dc.identifier.uri
http://hdl.handle.net/11336/8345
dc.description.abstract
Ceftaroline, a recently approved β-lactam antibiotic for treatment of infections by methicillinresistant Staphylococcus aureus (MRSA), is able to inhibit penicillin-binding protein 2a (PBP2a) by triggering an allosteric conformational change that leads to the opening of the active site. The opened active site is now vulnerable to inhibition by a second molecule of ceftaroline, an event that impairs cell-wall biosynthesis and leads to bacterial death. The triggering of the allosteric effect takes place by binding of the first antibiotic molecule 60 Å away from the active site of PBP2a within the core of the allosteric site. We document, by kinetic studies and by determination of three X-ray structures of the mutant variants of PBP2a that result in resistance to ceftaroline, that the effect of these clinical mutants is the disruption of the allosteric trigger in this important protein in MRSA. This is an unprecedented mechanism for antibiotic resistance.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Staphylococcus Aureus (Mrsa)
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Penicillin-Binding Protein 2a
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Ceftaroline
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Antibiotic Resistance
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Disruption of Allosteric Response as an Unprecedented Mechanism of Resistance to Antibiotics
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-11-18T15:20:25Z
dc.journal.volume
136
dc.journal.number
28
dc.journal.pagination
9814-9817
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Fishovitz, Jennifer. University of Notre Dame. Department of Chemistry and Biochemistry; Estados Unidos
dc.description.fil
Fil: Rojas Altuve, Alzoray. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España
dc.description.fil
Fil: Otero, Lisandro Horacio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
dc.description.fil
Fil: Dawley, Matthew. University of Notre Dame. Department of Chemistry and Biochemistry; Estados Unidos
dc.description.fil
Fil: Carrasco López, Cesar. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España
dc.description.fil
Fil: Chang, Mayland. University of Notre Dame. Department of Chemistry and Biochemistry; Estados Unidos
dc.description.fil
Fil: Hermoso, Juan Antonio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España
dc.description.fil
Fil: Mobashery, Shahriar. University of Notre Dame. Department of Chemistry and Biochemistry; Estados Unidos
dc.journal.title
Journal Of The American Chemical Society
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/full/10.1021/ja5030657
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/ja5030657
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