X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase
- Autores
- Risso, Valeria Alejandra; Acierno, Juan Pablo; Capaldi, Stefano; Monaco, Hugo L.; Ermacora, Mario Roberto
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- β-lactamases confer antibiotic resistance, one of the most serious world-wide health problems, and are an excellent theoretical and experimental model in the study of protein structure, dynamics and evolution. Bacillus licheniformis exo-small penicillinase (ESP) is a Class-A β-lactamase with three tryptophan residues located in the protein core. Here, we report the 1.7-Å resolution X-ray structure, catalytic parameters, and thermodynamic stability of ESPΔW, an engineered mutant of ESP in which phenylalanine replaces the wild-type tryptophan residues. The structure revealed no qualitative conformational changes compared with thirteen previously reported structures of B. licheniformis β-lactamases (RMSD = 0.4-1.2 Å). However, a closer scrutiny showed that the mutations result in an overall more compact structure, with most atoms shifted toward the geometric center of the molecule. Thus, ESPΔW has a significantly smaller radius of gyration (Rg) than the other B. licheniformis β-lactamases characterized so far. Indeed, ESPΔW has the smallest Rg among 126 Class-A β-lactamases in the Protein Data Bank (PDB). Other measures of compactness, like the number of atoms in fixed volumes and the number and average of noncovalent distances, confirmed the effect. ESPΔW proves that the compactness of the native state can be enhanced by protein engineering and establishes a new lower limit to the compactness of the Class-A β-lactamase fold. As the condensation achieved by the native state is a paramount notion in protein folding, this result may contribute to a better understanding of how the sequence determines the conformational variability and thermodynamic stability of a given fold.
Fil: Risso, Valeria Alejandra. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Acierno, Juan Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Capaldi, Stefano. Universita di Verona; Italia
Fil: Monaco, Hugo L.. Universita di Verona; Italia
Fil: Ermacora, Mario Roberto. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina - Materia
-
Β-LACTAM
B. LICHENIFORMIS
PENICILLINASE
PROTEIN COMPACTNESS
PROTEIN ENGINEERING
PROTEIN FOLDING
PROTEIN PACKING
RADIUS OF GYRATION
SITE-SPECIFIC MUTAGENESIS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/189311
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/189311 |
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CONICET Digital (CONICET) |
spelling |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamaseRisso, Valeria AlejandraAcierno, Juan PabloCapaldi, StefanoMonaco, Hugo L.Ermacora, Mario RobertoΒ-LACTAMB. LICHENIFORMISPENICILLINASEPROTEIN COMPACTNESSPROTEIN ENGINEERINGPROTEIN FOLDINGPROTEIN PACKINGRADIUS OF GYRATIONSITE-SPECIFIC MUTAGENESIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1β-lactamases confer antibiotic resistance, one of the most serious world-wide health problems, and are an excellent theoretical and experimental model in the study of protein structure, dynamics and evolution. Bacillus licheniformis exo-small penicillinase (ESP) is a Class-A β-lactamase with three tryptophan residues located in the protein core. Here, we report the 1.7-Å resolution X-ray structure, catalytic parameters, and thermodynamic stability of ESPΔW, an engineered mutant of ESP in which phenylalanine replaces the wild-type tryptophan residues. The structure revealed no qualitative conformational changes compared with thirteen previously reported structures of B. licheniformis β-lactamases (RMSD = 0.4-1.2 Å). However, a closer scrutiny showed that the mutations result in an overall more compact structure, with most atoms shifted toward the geometric center of the molecule. Thus, ESPΔW has a significantly smaller radius of gyration (Rg) than the other B. licheniformis β-lactamases characterized so far. Indeed, ESPΔW has the smallest Rg among 126 Class-A β-lactamases in the Protein Data Bank (PDB). Other measures of compactness, like the number of atoms in fixed volumes and the number and average of noncovalent distances, confirmed the effect. ESPΔW proves that the compactness of the native state can be enhanced by protein engineering and establishes a new lower limit to the compactness of the Class-A β-lactamase fold. As the condensation achieved by the native state is a paramount notion in protein folding, this result may contribute to a better understanding of how the sequence determines the conformational variability and thermodynamic stability of a given fold.Fil: Risso, Valeria Alejandra. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Acierno, Juan Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Capaldi, Stefano. Universita di Verona; ItaliaFil: Monaco, Hugo L.. Universita di Verona; ItaliaFil: Ermacora, Mario Roberto. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaJohn Wiley & Sons2012-07info: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/11336/189311Risso, Valeria Alejandra; Acierno, Juan Pablo; Capaldi, Stefano; Monaco, Hugo L.; Ermacora, Mario Roberto; X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase; John Wiley & Sons; Protein Science; 21; 7; 7-2012; 964-9760961-8368CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/pro.2076info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.2076info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:51Zoai:ri.conicet.gov.ar:11336/189311instacron: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 09:41:51.917CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase |
title |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase |
spellingShingle |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase Risso, Valeria Alejandra Β-LACTAM B. LICHENIFORMIS PENICILLINASE PROTEIN COMPACTNESS PROTEIN ENGINEERING PROTEIN FOLDING PROTEIN PACKING RADIUS OF GYRATION SITE-SPECIFIC MUTAGENESIS |
title_short |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase |
title_full |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase |
title_fullStr |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase |
title_full_unstemmed |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase |
title_sort |
X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase |
dc.creator.none.fl_str_mv |
Risso, Valeria Alejandra Acierno, Juan Pablo Capaldi, Stefano Monaco, Hugo L. Ermacora, Mario Roberto |
author |
Risso, Valeria Alejandra |
author_facet |
Risso, Valeria Alejandra Acierno, Juan Pablo Capaldi, Stefano Monaco, Hugo L. Ermacora, Mario Roberto |
author_role |
author |
author2 |
Acierno, Juan Pablo Capaldi, Stefano Monaco, Hugo L. Ermacora, Mario Roberto |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
Β-LACTAM B. LICHENIFORMIS PENICILLINASE PROTEIN COMPACTNESS PROTEIN ENGINEERING PROTEIN FOLDING PROTEIN PACKING RADIUS OF GYRATION SITE-SPECIFIC MUTAGENESIS |
topic |
Β-LACTAM B. LICHENIFORMIS PENICILLINASE PROTEIN COMPACTNESS PROTEIN ENGINEERING PROTEIN FOLDING PROTEIN PACKING RADIUS OF GYRATION SITE-SPECIFIC MUTAGENESIS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
β-lactamases confer antibiotic resistance, one of the most serious world-wide health problems, and are an excellent theoretical and experimental model in the study of protein structure, dynamics and evolution. Bacillus licheniformis exo-small penicillinase (ESP) is a Class-A β-lactamase with three tryptophan residues located in the protein core. Here, we report the 1.7-Å resolution X-ray structure, catalytic parameters, and thermodynamic stability of ESPΔW, an engineered mutant of ESP in which phenylalanine replaces the wild-type tryptophan residues. The structure revealed no qualitative conformational changes compared with thirteen previously reported structures of B. licheniformis β-lactamases (RMSD = 0.4-1.2 Å). However, a closer scrutiny showed that the mutations result in an overall more compact structure, with most atoms shifted toward the geometric center of the molecule. Thus, ESPΔW has a significantly smaller radius of gyration (Rg) than the other B. licheniformis β-lactamases characterized so far. Indeed, ESPΔW has the smallest Rg among 126 Class-A β-lactamases in the Protein Data Bank (PDB). Other measures of compactness, like the number of atoms in fixed volumes and the number and average of noncovalent distances, confirmed the effect. ESPΔW proves that the compactness of the native state can be enhanced by protein engineering and establishes a new lower limit to the compactness of the Class-A β-lactamase fold. As the condensation achieved by the native state is a paramount notion in protein folding, this result may contribute to a better understanding of how the sequence determines the conformational variability and thermodynamic stability of a given fold. Fil: Risso, Valeria Alejandra. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Acierno, Juan Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Capaldi, Stefano. Universita di Verona; Italia Fil: Monaco, Hugo L.. Universita di Verona; Italia Fil: Ermacora, Mario Roberto. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina |
description |
β-lactamases confer antibiotic resistance, one of the most serious world-wide health problems, and are an excellent theoretical and experimental model in the study of protein structure, dynamics and evolution. Bacillus licheniformis exo-small penicillinase (ESP) is a Class-A β-lactamase with three tryptophan residues located in the protein core. Here, we report the 1.7-Å resolution X-ray structure, catalytic parameters, and thermodynamic stability of ESPΔW, an engineered mutant of ESP in which phenylalanine replaces the wild-type tryptophan residues. The structure revealed no qualitative conformational changes compared with thirteen previously reported structures of B. licheniformis β-lactamases (RMSD = 0.4-1.2 Å). However, a closer scrutiny showed that the mutations result in an overall more compact structure, with most atoms shifted toward the geometric center of the molecule. Thus, ESPΔW has a significantly smaller radius of gyration (Rg) than the other B. licheniformis β-lactamases characterized so far. Indeed, ESPΔW has the smallest Rg among 126 Class-A β-lactamases in the Protein Data Bank (PDB). Other measures of compactness, like the number of atoms in fixed volumes and the number and average of noncovalent distances, confirmed the effect. ESPΔW proves that the compactness of the native state can be enhanced by protein engineering and establishes a new lower limit to the compactness of the Class-A β-lactamase fold. As the condensation achieved by the native state is a paramount notion in protein folding, this result may contribute to a better understanding of how the sequence determines the conformational variability and thermodynamic stability of a given fold. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-07 |
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/11336/189311 Risso, Valeria Alejandra; Acierno, Juan Pablo; Capaldi, Stefano; Monaco, Hugo L.; Ermacora, Mario Roberto; X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase; John Wiley & Sons; Protein Science; 21; 7; 7-2012; 964-976 0961-8368 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/189311 |
identifier_str_mv |
Risso, Valeria Alejandra; Acierno, Juan Pablo; Capaldi, Stefano; Monaco, Hugo L.; Ermacora, Mario Roberto; X-ray evidence of a native state with increased compactness populated by tryptophan-less B. licheniformis β-lactamase; John Wiley & Sons; Protein Science; 21; 7; 7-2012; 964-976 0961-8368 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://onlinelibrary.wiley.com/doi/10.1002/pro.2076 info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.2076 |
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 |
John Wiley & Sons |
publisher.none.fl_str_mv |
John Wiley & Sons |
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 |
_version_ |
1844613320225587200 |
score |
13.070432 |