Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii

Autores
Verma, Vidhu; Testero, Sebastian Andres; Amini, Kaveh; Wei, William; Liu, Jerome; Balachandran, Naresh; Monoharan, Tharseekan; Stynes, Siobhan; Kotra, Lakshmi P.; Golemi-Kotra, Dasantila
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Carbapenem-hydrolyzing class D β-lactamases (CHDLs) represent an emerging antibiotic resistance mechanism encountered among the most opportunistic Gram-negative bacterial pathogens. We report here the substrate kinetics and mechanistic characterization of a prominent CHDL, the OXA-58 enzyme, from Acinetobacter baumannii. OXA-58 uses a carbamylated lysine to activate the nucleophilic serine used for β-lactam hydrolysis. The deacylating water molecule approaches the acyl-enzyme species, anchored at this serine (Ser-83), from the α-face. Our data show that OXA-58 retains the catalytic machinery found in class D β-lactamases, of which OXA-10 is representative. Comparison of the homology model of OXA-58 and the recently solved crystal structures of OXA-24 and OXA-48 with the OXA-10 crystal structure suggests that these CHDLs have evolved the ability to hydrolyze imipenem, an important carbapenem in clinical use, by subtle structural changes in the active site. These changes may contribute to tighter binding of imipenem to the active site and removal of steric hindrances from the path of the deacylating water molecule.
Fil: Verma, Vidhu. University of York; Reino Unido
Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Amini, Kaveh. University of York; Reino Unido
Fil: Wei, William. University of Toronto; Canadá
Fil: Liu, Jerome. University of York; Reino Unido
Fil: Balachandran, Naresh. University of York; Reino Unido
Fil: Monoharan, Tharseekan. University of York; Reino Unido
Fil: Stynes, Siobhan. University of York; Reino Unido
Fil: Kotra, Lakshmi P.. University of Toronto; Canadá
Fil: Golemi-Kotra, Dasantila. University of York; Reino Unido
Materia
OXA-58
Carbapenem
β-lactamase
Antibiotic resistance
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:11336/133262
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/133262
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumanniiVerma, VidhuTestero, Sebastian AndresAmini, KavehWei, WilliamLiu, JeromeBalachandran, NareshMonoharan, TharseekanStynes, SiobhanKotra, Lakshmi P.Golemi-Kotra, DasantilaOXA-58Carbapenemβ-lactamaseAntibiotic resistancehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Carbapenem-hydrolyzing class D β-lactamases (CHDLs) represent an emerging antibiotic resistance mechanism encountered among the most opportunistic Gram-negative bacterial pathogens. We report here the substrate kinetics and mechanistic characterization of a prominent CHDL, the OXA-58 enzyme, from Acinetobacter baumannii. OXA-58 uses a carbamylated lysine to activate the nucleophilic serine used for β-lactam hydrolysis. The deacylating water molecule approaches the acyl-enzyme species, anchored at this serine (Ser-83), from the α-face. Our data show that OXA-58 retains the catalytic machinery found in class D β-lactamases, of which OXA-10 is representative. Comparison of the homology model of OXA-58 and the recently solved crystal structures of OXA-24 and OXA-48 with the OXA-10 crystal structure suggests that these CHDLs have evolved the ability to hydrolyze imipenem, an important carbapenem in clinical use, by subtle structural changes in the active site. These changes may contribute to tighter binding of imipenem to the active site and removal of steric hindrances from the path of the deacylating water molecule.Fil: Verma, Vidhu. University of York; Reino UnidoFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Amini, Kaveh. University of York; Reino UnidoFil: Wei, William. University of Toronto; CanadáFil: Liu, Jerome. University of York; Reino UnidoFil: Balachandran, Naresh. University of York; Reino UnidoFil: Monoharan, Tharseekan. University of York; Reino UnidoFil: Stynes, Siobhan. University of York; Reino UnidoFil: Kotra, Lakshmi P.. University of Toronto; CanadáFil: Golemi-Kotra, Dasantila. University of York; Reino UnidoAmerican Society for Biochemistry and Molecular Biology2011-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/133262Verma, Vidhu; Testero, Sebastian Andres; Amini, Kaveh; Wei, William; Liu, Jerome; et al.; Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 286; 43; 10-2011; 37292-373031083-351X0021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/reference/url/http://www.jbc.org/content/suppl/2011/08/30/M111.280115.DC1.htmlinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199476/info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M111.280115info:eu-repo/semantics/altIdentifier/url/https://www.jbc.org/article/S0021-9258(20)50755-2/fulltextinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:01Zoai:ri.conicet.gov.ar:11336/133262instacron: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:34982025-09-03 09:57:02.255CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
title Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
spellingShingle Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
Verma, Vidhu
OXA-58
Carbapenem
β-lactamase
Antibiotic resistance
title_short Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
title_full Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
title_fullStr Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
title_full_unstemmed Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
title_sort Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii
dc.creator.none.fl_str_mv Verma, Vidhu
Testero, Sebastian Andres
Amini, Kaveh
Wei, William
Liu, Jerome
Balachandran, Naresh
Monoharan, Tharseekan
Stynes, Siobhan
Kotra, Lakshmi P.
Golemi-Kotra, Dasantila
author Verma, Vidhu
author_facet Verma, Vidhu
Testero, Sebastian Andres
Amini, Kaveh
Wei, William
Liu, Jerome
Balachandran, Naresh
Monoharan, Tharseekan
Stynes, Siobhan
Kotra, Lakshmi P.
Golemi-Kotra, Dasantila
author_role author
author2 Testero, Sebastian Andres
Amini, Kaveh
Wei, William
Liu, Jerome
Balachandran, Naresh
Monoharan, Tharseekan
Stynes, Siobhan
Kotra, Lakshmi P.
Golemi-Kotra, Dasantila
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv OXA-58
Carbapenem
β-lactamase
Antibiotic resistance
topic OXA-58
Carbapenem
β-lactamase
Antibiotic resistance
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Carbapenem-hydrolyzing class D β-lactamases (CHDLs) represent an emerging antibiotic resistance mechanism encountered among the most opportunistic Gram-negative bacterial pathogens. We report here the substrate kinetics and mechanistic characterization of a prominent CHDL, the OXA-58 enzyme, from Acinetobacter baumannii. OXA-58 uses a carbamylated lysine to activate the nucleophilic serine used for β-lactam hydrolysis. The deacylating water molecule approaches the acyl-enzyme species, anchored at this serine (Ser-83), from the α-face. Our data show that OXA-58 retains the catalytic machinery found in class D β-lactamases, of which OXA-10 is representative. Comparison of the homology model of OXA-58 and the recently solved crystal structures of OXA-24 and OXA-48 with the OXA-10 crystal structure suggests that these CHDLs have evolved the ability to hydrolyze imipenem, an important carbapenem in clinical use, by subtle structural changes in the active site. These changes may contribute to tighter binding of imipenem to the active site and removal of steric hindrances from the path of the deacylating water molecule.
Fil: Verma, Vidhu. University of York; Reino Unido
Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Amini, Kaveh. University of York; Reino Unido
Fil: Wei, William. University of Toronto; Canadá
Fil: Liu, Jerome. University of York; Reino Unido
Fil: Balachandran, Naresh. University of York; Reino Unido
Fil: Monoharan, Tharseekan. University of York; Reino Unido
Fil: Stynes, Siobhan. University of York; Reino Unido
Fil: Kotra, Lakshmi P.. University of Toronto; Canadá
Fil: Golemi-Kotra, Dasantila. University of York; Reino Unido
description Carbapenem-hydrolyzing class D β-lactamases (CHDLs) represent an emerging antibiotic resistance mechanism encountered among the most opportunistic Gram-negative bacterial pathogens. We report here the substrate kinetics and mechanistic characterization of a prominent CHDL, the OXA-58 enzyme, from Acinetobacter baumannii. OXA-58 uses a carbamylated lysine to activate the nucleophilic serine used for β-lactam hydrolysis. The deacylating water molecule approaches the acyl-enzyme species, anchored at this serine (Ser-83), from the α-face. Our data show that OXA-58 retains the catalytic machinery found in class D β-lactamases, of which OXA-10 is representative. Comparison of the homology model of OXA-58 and the recently solved crystal structures of OXA-24 and OXA-48 with the OXA-10 crystal structure suggests that these CHDLs have evolved the ability to hydrolyze imipenem, an important carbapenem in clinical use, by subtle structural changes in the active site. These changes may contribute to tighter binding of imipenem to the active site and removal of steric hindrances from the path of the deacylating water molecule.
publishDate 2011
dc.date.none.fl_str_mv 2011-10
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/11336/133262
Verma, Vidhu; Testero, Sebastian Andres; Amini, Kaveh; Wei, William; Liu, Jerome; et al.; Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 286; 43; 10-2011; 37292-37303
1083-351X
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/133262
identifier_str_mv Verma, Vidhu; Testero, Sebastian Andres; Amini, Kaveh; Wei, William; Liu, Jerome; et al.; Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D β-lactamase from Acinetobacter baumannii; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 286; 43; 10-2011; 37292-37303
1083-351X
0021-9258
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/reference/url/http://www.jbc.org/content/suppl/2011/08/30/M111.280115.DC1.html
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199476/
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M111.280115
info:eu-repo/semantics/altIdentifier/url/https://www.jbc.org/article/S0021-9258(20)50755-2/fulltext
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
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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 13.13397

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