Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods
Impacte
Scholar |
Altres documents de l'autoria: Sánchez-Tarín, María; Świderek, Katarzyna; Roca, Maite; Tuñón, Iñaki
Metadades
Mostra el registre complet de l'elementcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONMetadades
Títol
Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM MethodsData de publicació
2015Editor
American Chemical SocietyISSN
1520-6106; 1520-5207Cita bibliogràfica
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.Tipus de document
info:eu-repo/semantics/articleVersió de l'editorial
http://pubs.acs.org/doi/abs/10.1021/jp511147bVersió
info:eu-repo/semantics/acceptedVersionParaules clau / Matèries
Resum
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. [-]
Publicat a
The Journal of Physical Chemistry B, 2015, vol. 119, no 5Drets d'accés
Copyright © American Chemical Society
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info:eu-repo/semantics/openAccess
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info:eu-repo/semantics/openAccess
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