Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformatión for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanases
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Otros documentos de la autoría: Soliman, Mahmoud E. S.; Ruggiero, Giuseppe D.; Ruiz-Pernía, José Javier; Greig, Ian R.; Williams, Ian H.
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Título
Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformatión for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanasesAutoría
Fecha de publicación
2009Editor
Royal Society of ChemistryISSN
1477-0520Cita bibliográfica
SOLIMAN, Mahmoud ES, et al. Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformation for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanases. Organic & biomolecular chemistry, 2009, vol. 7, no 3, p. 460-468.Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://pubs.rsc.org/en/content/articlepdf/2009/ob/b814695k?page=searchVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Molecular dynamics simulations have been performed for non-covalent complexes of phenyl
b-xylobioside with the retaining endo-b-1,4-xylanase from B. circulans (BCX) and its Tyr69Phe mutant
using a hybrid QM/MM ... [+]
Molecular dynamics simulations have been performed for non-covalent complexes of phenyl
b-xylobioside with the retaining endo-b-1,4-xylanase from B. circulans (BCX) and its Tyr69Phe mutant
using a hybrid QM/MM methodology. A trajectory initiated for the wild-type enzyme–substrate
complex with the proximal xylose ring bound at the –1 subsite (adjacent to the scissile glycosidic bond)
in the 4C1 chair conformation shows spontaneous transformation to the 2,5B boat conformation, and
potential of mean force calculations indicate that the boat is ~30 kJ mol-1 lower in free energy than the
chair. Analogous simulations for the mutant lacking one oxygen atom confirm the key role of Tyr69 in
stabilizing the boat in preference to the 4C1 chair conformation, with a relative free energy difference of
about 20 kJ mol-1, by donating a hydrogen bond to the endocyclic oxygen of the proximal xylose ring.
QM/MM MD simulations for phenyl b-xyloside in water, with and without a propionate/propionic
acid pair to mimic the catalytic glutamate/glutamic acid pair of the enzyme, show the 4C1 chair to be
stable, although a hydrogen bond between the OH group at C2 of xylose and the propionate moiety
seems to provide some stabilization for the 2,5B conformation [-]
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Organic & biomolecular chemistry, 2009, v. 7Derechos de acceso
© Royal Society of Chemistry 2009
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