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dc.contributor.author
Borosky, Gabriela Leonor
dc.contributor.author
Lin, Susana
dc.date.available
2018-10-04T21:08:54Z
dc.date.issued
2011-10
dc.identifier.citation
Borosky, Gabriela Leonor; Lin, Susana; Computational modeling of the catalytic mechanism of human placental alkaline phosphatase (PLAP); American Chemical Society; Journal of Chemical Information and Modeling; 51; 10; 10-2011; 2538-2548
dc.identifier.issn
1549-9596
dc.identifier.uri
http://hdl.handle.net/11336/61731
dc.description.abstract
Alkaline phosphatases (APs) catalyze the hydrolysis and transphosphorylation of phosphate monoesters. Quantum mechanical, molecular dynamics, and molecular docking techniques were applied to computationally model the catalytic mechanism of human placental AP (PLAP). Kinetic and thermodynamic evaluations were performed for each reaction step. The functional significances of the more important residues within the active site were analyzed. The role of the metal ion at the metal binding site M3 was also examined. The calculated activation and reaction energy and free energy values obtained suggested the nucleophilic attack of the Ser92 alkoxide on the phosphorus atom of the substrate would be the rate-limiting step of the catalytic hydrolysis of alkyl phosphate monoesters by PLAP. The reactivities of the wild-type M3-Mg enzyme and the M3-Zn protein were compared, and the main difference observed was a change in the coordination number of the M3 metal for the M3-Zn enzyme. This modification in the active site structure lowered the free energy profile for the second chemical step of the catalytic mechanism (hydrolysis of the covalent phosphoserine intermediate). Consequently, a greater stabilization of the phosphoseryl moiety resulted in a small increment in the activation free energy of the phosphoserine hydrolysis reaction. These computational results suggest that the activation of APs by magnesium at the M3 site is caused by the preference of Mg2+ for octahedral coordination, which structurally stabilizes the active site into a catalytically most active conformation. The present theoretical results are in good agreement with previously reported experimental studies. © 2011 American Chemical Society.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Alkaline Phosphatase
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Quantum Chemistry
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Oniom Calculations
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Chemical Reactivity
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Otras Ciencias Químicas
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Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Computational modeling of the catalytic mechanism of human placental alkaline phosphatase (PLAP)
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-10-01T15:23:07Z
dc.journal.volume
51
dc.journal.number
10
dc.journal.pagination
2538-2548
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
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
dc.description.fil
Fil: Lin, Susana. National Health Research Institutes; República de China
dc.journal.title
Journal of Chemical Information and Modeling
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1021/ci200228s
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/ci200228s
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