Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases

Autores
Borosky, Gabriela Leonor
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alkaline phosphatases (APs) catalyze the hydrolysis and transphosphorylation of phosphate monoesters. The catalytic mechanism was examined by quantum-mechanical calculations using an active-site model based on the X-ray crystal structure of the human placental AP. Free energies of activation and of reaction for the catalytic steps were evaluated for a series of aryl and alkyl phosphate esters, and the computational results were compared with experimental values available in the literature. Mechanistic observations previously reported in experimental works were rationalized by the present theoretical study, particularly regarding the difference in the rate-determining step between aryl and alkyl phosphates. The formation rate of the covalent phosphoserine intermediate followed a linear free energy relationship (LFER) with the pKa of the leaving group. This LFER, which could be experimentally determined only for less reactive alkyl phosphates, was verified by the present calculations to apply for the entire set of aryl and alkyl phosphate substrates. (Chemical Equation Presented).
Fil: Borosky, Gabriela Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Materia
Enzymatic Catalysis
Alkaline Phosphatases
Quantum-Chemical Calculations
Catalytic Mechanism
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:11336/62334
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/62334
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Quantum-mechanical study on the catalytic mechanism of alkaline phosphatasesBorosky, Gabriela LeonorEnzymatic CatalysisAlkaline PhosphatasesQuantum-Chemical CalculationsCatalytic Mechanismhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Alkaline phosphatases (APs) catalyze the hydrolysis and transphosphorylation of phosphate monoesters. The catalytic mechanism was examined by quantum-mechanical calculations using an active-site model based on the X-ray crystal structure of the human placental AP. Free energies of activation and of reaction for the catalytic steps were evaluated for a series of aryl and alkyl phosphate esters, and the computational results were compared with experimental values available in the literature. Mechanistic observations previously reported in experimental works were rationalized by the present theoretical study, particularly regarding the difference in the rate-determining step between aryl and alkyl phosphates. The formation rate of the covalent phosphoserine intermediate followed a linear free energy relationship (LFER) with the pKa of the leaving group. This LFER, which could be experimentally determined only for less reactive alkyl phosphates, was verified by the present calculations to apply for the entire set of aryl and alkyl phosphate substrates. (Chemical Equation Presented).Fil: Borosky, Gabriela Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaAmerican Chemical Society2017-02-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/62334Borosky, Gabriela Leonor; Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases; American Chemical Society; Journal of Chemical Information and Modeling; 57; 3; 13-2-2017; 540-5491549-95961549-960XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.jcim.6b00755info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jcim.6b00755info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:19:10Zoai:ri.conicet.gov.ar:11336/62334instacron: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:34982025-09-10 13:19:10.952CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
title Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
spellingShingle Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
Borosky, Gabriela Leonor
Enzymatic Catalysis
Alkaline Phosphatases
Quantum-Chemical Calculations
Catalytic Mechanism
title_short Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
title_full Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
title_fullStr Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
title_full_unstemmed Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
title_sort Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases
dc.creator.none.fl_str_mv Borosky, Gabriela Leonor
author Borosky, Gabriela Leonor
author_facet Borosky, Gabriela Leonor
author_role author
dc.subject.none.fl_str_mv Enzymatic Catalysis
Alkaline Phosphatases
Quantum-Chemical Calculations
Catalytic Mechanism
topic Enzymatic Catalysis
Alkaline Phosphatases
Quantum-Chemical Calculations
Catalytic Mechanism
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alkaline phosphatases (APs) catalyze the hydrolysis and transphosphorylation of phosphate monoesters. The catalytic mechanism was examined by quantum-mechanical calculations using an active-site model based on the X-ray crystal structure of the human placental AP. Free energies of activation and of reaction for the catalytic steps were evaluated for a series of aryl and alkyl phosphate esters, and the computational results were compared with experimental values available in the literature. Mechanistic observations previously reported in experimental works were rationalized by the present theoretical study, particularly regarding the difference in the rate-determining step between aryl and alkyl phosphates. The formation rate of the covalent phosphoserine intermediate followed a linear free energy relationship (LFER) with the pKa of the leaving group. This LFER, which could be experimentally determined only for less reactive alkyl phosphates, was verified by the present calculations to apply for the entire set of aryl and alkyl phosphate substrates. (Chemical Equation Presented).
Fil: Borosky, Gabriela Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
description Alkaline phosphatases (APs) catalyze the hydrolysis and transphosphorylation of phosphate monoesters. The catalytic mechanism was examined by quantum-mechanical calculations using an active-site model based on the X-ray crystal structure of the human placental AP. Free energies of activation and of reaction for the catalytic steps were evaluated for a series of aryl and alkyl phosphate esters, and the computational results were compared with experimental values available in the literature. Mechanistic observations previously reported in experimental works were rationalized by the present theoretical study, particularly regarding the difference in the rate-determining step between aryl and alkyl phosphates. The formation rate of the covalent phosphoserine intermediate followed a linear free energy relationship (LFER) with the pKa of the leaving group. This LFER, which could be experimentally determined only for less reactive alkyl phosphates, was verified by the present calculations to apply for the entire set of aryl and alkyl phosphate substrates. (Chemical Equation Presented).
publishDate 2017
dc.date.none.fl_str_mv 2017-02-13
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/11336/62334
Borosky, Gabriela Leonor; Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases; American Chemical Society; Journal of Chemical Information and Modeling; 57; 3; 13-2-2017; 540-549
1549-9596
1549-960X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/62334
identifier_str_mv Borosky, Gabriela Leonor; Quantum-mechanical study on the catalytic mechanism of alkaline phosphatases; American Chemical Society; Journal of Chemical Information and Modeling; 57; 3; 13-2-2017; 540-549
1549-9596
1549-960X
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/acs.jcim.6b00755
info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jcim.6b00755
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 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 12.48226

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