Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3

Autores
Power, Pablo; Mercuri, Paola; Herman, Raphaël; Kerff, Frédéric; Gutkind, Gabriel Osvaldo; Dive, Georges; Galleni, Moreno; Charlier, Paulette; Sauvage, Eric
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: Our aim was to unravel the inactivation pathway of the class A β-lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. Methods: The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. Results: The analysis of the X-ray structure of the complex yielded by the reaction between clavulanate and BS3 indicates that the transient inactivated form, namely the cis-trans enamine complex, is hydrolysed to an ethane-imine ester covalently linked to the active site serine and a pentan-3-one-5-ol acid. It is the first time that this mechanism has been observed in an inactivated β-lactamase. Furthermore, the ionic interactions made by the carboxylic group of pentan-3-one-5-ol may provide an understanding of the decarboxylation process of the trans-enamine observed in the non-productive complex observed for the interaction between clavulanate and SHV-1 and Mycobacterium tuberculosis β-lactamase (Mtu). Conclusions: This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A β-lactamase/clavulanate adducts.
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Mercuri, Paola. Université de Liège; Bélgica
Fil: Herman, Raphaël. Université de Liège; Bélgica
Fil: Kerff, Frédéric. Université de Liège; Bélgica
Fil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
Fil: Dive, Georges. Université de Liège; Bélgica
Fil: Galleni, Moreno. Université de Liège; Bélgica
Fil: Charlier, Paulette. Université de Liège; Bélgica
Fil: Sauvage, Eric. Université de Liège; Bélgica
Materia
Β-LACTAMASE INACTIVATION
BACTERIAL RESISTANCE
CLAVULANATE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/112834
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/112834
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3Power, PabloMercuri, PaolaHerman, RaphaëlKerff, FrédéricGutkind, Gabriel OsvaldoDive, GeorgesGalleni, MorenoCharlier, PauletteSauvage, EricΒ-LACTAMASE INACTIVATIONBACTERIAL RESISTANCECLAVULANATEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Objectives: Our aim was to unravel the inactivation pathway of the class A β-lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. Methods: The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. Results: The analysis of the X-ray structure of the complex yielded by the reaction between clavulanate and BS3 indicates that the transient inactivated form, namely the cis-trans enamine complex, is hydrolysed to an ethane-imine ester covalently linked to the active site serine and a pentan-3-one-5-ol acid. It is the first time that this mechanism has been observed in an inactivated β-lactamase. Furthermore, the ionic interactions made by the carboxylic group of pentan-3-one-5-ol may provide an understanding of the decarboxylation process of the trans-enamine observed in the non-productive complex observed for the interaction between clavulanate and SHV-1 and Mycobacterium tuberculosis β-lactamase (Mtu). Conclusions: This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A β-lactamase/clavulanate adducts.Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Mercuri, Paola. Université de Liège; BélgicaFil: Herman, Raphaël. Université de Liège; BélgicaFil: Kerff, Frédéric. Université de Liège; BélgicaFil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Dive, Georges. Université de Liège; BélgicaFil: Galleni, Moreno. Université de Liège; BélgicaFil: Charlier, Paulette. Université de Liège; BélgicaFil: Sauvage, Eric. Université de Liège; BélgicaOxford University Press2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112834Power, Pablo; Mercuri, Paola; Herman, Raphaël; Kerff, Frédéric; Gutkind, Gabriel Osvaldo; et al.; Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3; Oxford University Press; Journal of Antimicrobial Chemotherapy; 67; 10; 10-2012; 2379-23870305-7453CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dks231info:eu-repo/semantics/altIdentifier/doi/10.1093/jac/dks231info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:47:45Zoai:ri.conicet.gov.ar:11336/112834instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:47:45.361CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
title Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
spellingShingle Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
Power, Pablo
Β-LACTAMASE INACTIVATION
BACTERIAL RESISTANCE
CLAVULANATE
title_short Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
title_full Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
title_fullStr Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
title_full_unstemmed Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
title_sort Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3
dc.creator.none.fl_str_mv Power, Pablo
Mercuri, Paola
Herman, Raphaël
Kerff, Frédéric
Gutkind, Gabriel Osvaldo
Dive, Georges
Galleni, Moreno
Charlier, Paulette
Sauvage, Eric
author Power, Pablo
author_facet Power, Pablo
Mercuri, Paola
Herman, Raphaël
Kerff, Frédéric
Gutkind, Gabriel Osvaldo
Dive, Georges
Galleni, Moreno
Charlier, Paulette
Sauvage, Eric
author_role author
author2 Mercuri, Paola
Herman, Raphaël
Kerff, Frédéric
Gutkind, Gabriel Osvaldo
Dive, Georges
Galleni, Moreno
Charlier, Paulette
Sauvage, Eric
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Β-LACTAMASE INACTIVATION
BACTERIAL RESISTANCE
CLAVULANATE
topic Β-LACTAMASE INACTIVATION
BACTERIAL RESISTANCE
CLAVULANATE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Objectives: Our aim was to unravel the inactivation pathway of the class A β-lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. Methods: The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. Results: The analysis of the X-ray structure of the complex yielded by the reaction between clavulanate and BS3 indicates that the transient inactivated form, namely the cis-trans enamine complex, is hydrolysed to an ethane-imine ester covalently linked to the active site serine and a pentan-3-one-5-ol acid. It is the first time that this mechanism has been observed in an inactivated β-lactamase. Furthermore, the ionic interactions made by the carboxylic group of pentan-3-one-5-ol may provide an understanding of the decarboxylation process of the trans-enamine observed in the non-productive complex observed for the interaction between clavulanate and SHV-1 and Mycobacterium tuberculosis β-lactamase (Mtu). Conclusions: This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A β-lactamase/clavulanate adducts.
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Mercuri, Paola. Université de Liège; Bélgica
Fil: Herman, Raphaël. Université de Liège; Bélgica
Fil: Kerff, Frédéric. Université de Liège; Bélgica
Fil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
Fil: Dive, Georges. Université de Liège; Bélgica
Fil: Galleni, Moreno. Université de Liège; Bélgica
Fil: Charlier, Paulette. Université de Liège; Bélgica
Fil: Sauvage, Eric. Université de Liège; Bélgica
description Objectives: Our aim was to unravel the inactivation pathway of the class A β-lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. Methods: The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. Results: The analysis of the X-ray structure of the complex yielded by the reaction between clavulanate and BS3 indicates that the transient inactivated form, namely the cis-trans enamine complex, is hydrolysed to an ethane-imine ester covalently linked to the active site serine and a pentan-3-one-5-ol acid. It is the first time that this mechanism has been observed in an inactivated β-lactamase. Furthermore, the ionic interactions made by the carboxylic group of pentan-3-one-5-ol may provide an understanding of the decarboxylation process of the trans-enamine observed in the non-productive complex observed for the interaction between clavulanate and SHV-1 and Mycobacterium tuberculosis β-lactamase (Mtu). Conclusions: This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A β-lactamase/clavulanate adducts.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/112834
Power, Pablo; Mercuri, Paola; Herman, Raphaël; Kerff, Frédéric; Gutkind, Gabriel Osvaldo; et al.; Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3; Oxford University Press; Journal of Antimicrobial Chemotherapy; 67; 10; 10-2012; 2379-2387
0305-7453
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112834
identifier_str_mv Power, Pablo; Mercuri, Paola; Herman, Raphaël; Kerff, Frédéric; Gutkind, Gabriel Osvaldo; et al.; Novel fragments of clavulanate observed in the structure of the class A β-lactamase from Bacillus licheniformis BS3; Oxford University Press; Journal of Antimicrobial Chemotherapy; 67; 10; 10-2012; 2379-2387
0305-7453
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dks231
info:eu-repo/semantics/altIdentifier/doi/10.1093/jac/dks231
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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