Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods
Impacto
Scholar |
Otros documentos de la autoría: Sánchez-Tarín, María; Świderek, Katarzyna; Roca, Maite; Tuñón, Iñaki
Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONMetadatos
Título
Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM MethodsFecha de publicación
2015Editor
American Chemical SocietyISSN
1520-6106; 1520-5207Cita bibliográfica
SÁNCHEZ-TARÍN, María, et al. Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods. The Journal of Physical Chemistry B, 2015, vol. 119, no 5, p. 1899-1911.Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://pubs.acs.org/doi/abs/10.1021/jp511147bVersión
info:eu-repo/semantics/acceptedVersionPalabras clave / Materias
Resumen
The promiscuous activity of the enzyme o-succinylbenzoate synthase (OSBS) from the actinobacteria Amycolatopsis is investigated by means of QM/MM methods, using both density functional theory and semiempirical Hamil ... [+]
The promiscuous activity of the enzyme o-succinylbenzoate synthase (OSBS) from the actinobacteria Amycolatopsis is investigated by means of QM/MM methods, using both density functional theory and semiempirical Hamiltonians. This enzyme catalyzes not only the dehydration of 2-succinyl-6R-hydroxy-2,4-cyclohexadiene-1R-carboxylate but also catalyzes racemization of different acylamino acids, with N-succinyl-R-phenylglycine being the best substrate. We investigated the molecular mechanisms for both reactions exploring the potential energy surface. Then, molecular dynamics simulations were performed to obtain the free energy profiles and the averaged interaction energies of enzymatic residues with the reacting system. Our results confirm the plausibility of the reaction mechanisms proposed in the literature, with a good agreement between theoretical and experimentally derived activation free energies. Our simulations unravel the role played by the different residues in each of the two possible reactions. The presence of flexible loops in the active site and the selection of structural modifications in the substrate seem to be key elements to promote the promiscuity of this enzyme. [-]
Publicado en
The Journal of Physical Chemistry B, 2015, vol. 119, no 5Derechos de acceso
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