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dc.contributor.authorBlanco Rodríguez, Beatriz
dc.contributor.authorSedes, Antía
dc.contributor.authorPeón López, Antonio
dc.contributor.authorOtero Casas, José Manuel
dc.contributor.authorRaaij, Mark J. van
dc.contributor.authorThompson, Paul
dc.contributor.authorHawkins, Alastair R.
dc.contributor.authorGonzález Bello, Concepción
dc.date.accessioned2018-07-03T09:57:39Z
dc.date.available2018-07-03T09:57:39Z
dc.date.issued2014
dc.identifier.citationBlanco, B., Sedes, A., Peón, A., Otero, J., van Raaij, M., & Thompson, P. et al. (2014). Exploring the Water-Binding Pocket of the Type II Dehydroquinase Enzyme in the Structure-Based Design of Inhibitors. Journal Of Medicinal Chemistry, 57(8), 3494-3510. doi: 10.1021/jm500175z
dc.identifier.issn0022-2623
dc.identifier.urihttp://hdl.handle.net/10347/16932
dc.description.abstractStructural and computational studies to explore the WAT1 binding pocket in the structure-based design of inhibitors against the type II dehydroquinase (DHQ2) enzyme are reported. The crystal structures of DHQ2 from M. tuberculosis in complex with four of the reported compounds are described. The electrostatic interaction observed between the guanidinium group of the essential arginine and the carboxylate group of one of the inhibitors in the reported crystal structures supports the recently suggested role of this arginine as the residue that triggers the release of the product from the active site. The results of the structural and molecular dynamics simulation studies revealed that the inhibitory potency is favored by promoting interactions with WAT1 and the residues located within this pocket and, more importantly, by avoiding situations where the ligands occupy the WAT1 binding pocket. The new insights can be used to advantage in the structure-based design of inhibitors
dc.description.sponsorshipFinancial support from the Spanish Ministry of Science and Innovation (Grant SAF2010-15076) and the Xunta de Galicia (Grant GRC2013/041) is gratefully acknowledged. B.B. and A.P. thank the Spanish Ministry of Education for their respective FPU fellowships. A.S. thanks the Spanish Ministry of Economy and Competitiveness for her FPI fellowship. J.M.O. thanks the Xunta de Galicia for a Plan I2C postdoctoral fellowship
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.relationinfo:eu-repo/grantAgreement/MICINN/Plan Nacional de I+D+i 2008-2011/SAF2010-15076/ES/ANTIBIOTICOS INHIBIDORES DE NOVEDOSAS DIANAS TERAPEUTICAS: DISEÑO, SINTESIS Y EVALUACION BIOLOGICA
dc.rights© 2014 American Chemical Society
dc.titleExploring the Water-Binding Pocket of the Type II Dehydroquinase Enzyme in the Structure-Based Design of Inhibitors
dc.typeinfo:eu-repo/semantics/article
dc.identifier.DOI10.1021/jm500175z
dc.relation.publisherversionhttps://doi.org/10.1021/jm500175z
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.identifier.e-issn1520-4804
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.contributor.affiliationUniversidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Bioquímica e Bioloxía Molecular
dc.description.peerreviewedSI


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