Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases

Autores
Gonzalez, Javier Marcelo; Buschiazzo, Alejandro; Vila, Alejandro Jose
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Subclass B1 β-lactamases are Zn(II)-dependent hydrolases that confer bacterial resistance to most clinically useful β-lactam antibiotics. The enzyme BcII from Bacillus cereus is a prototypical enzyme that belongs to this group, the first Zn(II)-dependent β-lactamase to be discovered. Crucial aspects of the BcII catalytic mechanism and metal binding mode have been assessed mostly on the Co(II)-substituted surrogate. Here we report a high-resolution structure of Co(II)-BcII, revealing a metal coordination geometry identical to that of the native zinc enzyme. In addition, a high-resolution structure of the apoenzyme, together with structures with different degrees of metal occupancy and oxidation levels of a conserved Cys ligand, discloses a considerable mobility of two loops containing four metal ligands (namely, regions His116−Arg121 and Gly219−Cys221). This flexibility is expected to assist in the structural rearrangement of the metal sites during catalytic turnover, which, along with the coordination geometry adaptability of Zn(II) ions, grants the interaction with a variety of substrates, a characteristic feature of B1 metallo-β-lactamases.
Fil: Gonzalez, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Buschiazzo, Alejandro. Instituto Pasteur de Montevideo; Uruguay
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Materia
Lactamase
Antibiotic
Resistance
Zinc
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:11336/278368
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/278368
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamasesGonzalez, Javier MarceloBuschiazzo, AlejandroVila, Alejandro JoseLactamaseAntibioticResistanceZinchttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Subclass B1 β-lactamases are Zn(II)-dependent hydrolases that confer bacterial resistance to most clinically useful β-lactam antibiotics. The enzyme BcII from Bacillus cereus is a prototypical enzyme that belongs to this group, the first Zn(II)-dependent β-lactamase to be discovered. Crucial aspects of the BcII catalytic mechanism and metal binding mode have been assessed mostly on the Co(II)-substituted surrogate. Here we report a high-resolution structure of Co(II)-BcII, revealing a metal coordination geometry identical to that of the native zinc enzyme. In addition, a high-resolution structure of the apoenzyme, together with structures with different degrees of metal occupancy and oxidation levels of a conserved Cys ligand, discloses a considerable mobility of two loops containing four metal ligands (namely, regions His116−Arg121 and Gly219−Cys221). This flexibility is expected to assist in the structural rearrangement of the metal sites during catalytic turnover, which, along with the coordination geometry adaptability of Zn(II) ions, grants the interaction with a variety of substrates, a characteristic feature of B1 metallo-β-lactamases.Fil: Gonzalez, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Buschiazzo, Alejandro. Instituto Pasteur de Montevideo; UruguayFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaAmerican Chemical Society2010-09info: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/11336/278368Gonzalez, Javier Marcelo; Buschiazzo, Alejandro; Vila, Alejandro Jose; Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases; American Chemical Society; Biochemistry; 49; 36; 9-2010; 7930-79380006-2960CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/bi100894rinfo:eu-repo/semantics/altIdentifier/doi/10.1021/bi100894rinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-01-08T13:10:46Zoai:ri.conicet.gov.ar:11336/278368instacron: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:34982026-01-08 13:10:47.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
title Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
spellingShingle Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
Gonzalez, Javier Marcelo
Lactamase
Antibiotic
Resistance
Zinc
title_short Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
title_full Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
title_fullStr Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
title_full_unstemmed Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
title_sort Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases
dc.creator.none.fl_str_mv Gonzalez, Javier Marcelo
Buschiazzo, Alejandro
Vila, Alejandro Jose
author Gonzalez, Javier Marcelo
author_facet Gonzalez, Javier Marcelo
Buschiazzo, Alejandro
Vila, Alejandro Jose
author_role author
author2 Buschiazzo, Alejandro
Vila, Alejandro Jose
author2_role author
author
dc.subject.none.fl_str_mv Lactamase
Antibiotic
Resistance
Zinc
topic Lactamase
Antibiotic
Resistance
Zinc
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Subclass B1 β-lactamases are Zn(II)-dependent hydrolases that confer bacterial resistance to most clinically useful β-lactam antibiotics. The enzyme BcII from Bacillus cereus is a prototypical enzyme that belongs to this group, the first Zn(II)-dependent β-lactamase to be discovered. Crucial aspects of the BcII catalytic mechanism and metal binding mode have been assessed mostly on the Co(II)-substituted surrogate. Here we report a high-resolution structure of Co(II)-BcII, revealing a metal coordination geometry identical to that of the native zinc enzyme. In addition, a high-resolution structure of the apoenzyme, together with structures with different degrees of metal occupancy and oxidation levels of a conserved Cys ligand, discloses a considerable mobility of two loops containing four metal ligands (namely, regions His116−Arg121 and Gly219−Cys221). This flexibility is expected to assist in the structural rearrangement of the metal sites during catalytic turnover, which, along with the coordination geometry adaptability of Zn(II) ions, grants the interaction with a variety of substrates, a characteristic feature of B1 metallo-β-lactamases.
Fil: Gonzalez, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Buschiazzo, Alejandro. Instituto Pasteur de Montevideo; Uruguay
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
description Subclass B1 β-lactamases are Zn(II)-dependent hydrolases that confer bacterial resistance to most clinically useful β-lactam antibiotics. The enzyme BcII from Bacillus cereus is a prototypical enzyme that belongs to this group, the first Zn(II)-dependent β-lactamase to be discovered. Crucial aspects of the BcII catalytic mechanism and metal binding mode have been assessed mostly on the Co(II)-substituted surrogate. Here we report a high-resolution structure of Co(II)-BcII, revealing a metal coordination geometry identical to that of the native zinc enzyme. In addition, a high-resolution structure of the apoenzyme, together with structures with different degrees of metal occupancy and oxidation levels of a conserved Cys ligand, discloses a considerable mobility of two loops containing four metal ligands (namely, regions His116−Arg121 and Gly219−Cys221). This flexibility is expected to assist in the structural rearrangement of the metal sites during catalytic turnover, which, along with the coordination geometry adaptability of Zn(II) ions, grants the interaction with a variety of substrates, a characteristic feature of B1 metallo-β-lactamases.
publishDate 2010
dc.date.none.fl_str_mv 2010-09
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/11336/278368
Gonzalez, Javier Marcelo; Buschiazzo, Alejandro; Vila, Alejandro Jose; Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases; American Chemical Society; Biochemistry; 49; 36; 9-2010; 7930-7938
0006-2960
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278368
identifier_str_mv Gonzalez, Javier Marcelo; Buschiazzo, Alejandro; Vila, Alejandro Jose; Evidence of Adaptability in Metal Coordination Geometry and Active-Site Loop Conformation among B1 Metallo-B-lactamases; American Chemical Society; Biochemistry; 49; 36; 9-2010; 7930-7938
0006-2960
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://pubs.acs.org/doi/10.1021/bi100894r
info:eu-repo/semantics/altIdentifier/doi/10.1021/bi100894r
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 American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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 12.747614

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