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dc.contributor.author
Fernandez, Ariel
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dc.date.available
2022-02-01T18:57:56Z
dc.date.issued
2019-06
dc.identifier.citation
Fernandez, Ariel; Protein structural defects enable pharmaceutical targeting while functionalizing the M2 proton channel; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 514; 1; 6-2019; 86-91
dc.identifier.issn
0006-291X
dc.identifier.uri
http://hdl.handle.net/11336/151094
dc.description.abstract
The influenza M2 (22–46) proton channel is therapeutically targetable and a prototype for proton transport across membranes. Conduction initiation, requiring a hydronium formed with exceptionally high pKa, remains nebulous. We tackle the problem by focusing on the dynamic interplay between protein structure and solvent interface. We identify two packing defects in the protein subunits that predict exactly the low and high-affinity drug-binding sites. The latter defect frustrates water coordination, enhancing water basicity and stabilizing the nearby hydronium that forms upon proton penetration in the channel. Thus, the trigger of proton conduction is directly related to the high-affinity binding site. The findings, in quantitative agreement with affinity measurements, are consistent with the targetable functional nature of protein packing defects. These findings enable the design of proton-conducting biomimetic materials, where the epistructure may be engineered to tune the basicity of interfacial water.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Inc Elsevier Science
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dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
HYDROGEN BOND
dc.subject
INFLUENZA VIRUS
dc.subject
PROTON CHANNEL
dc.subject
STRUCTURAL BIOLOGY
dc.subject
TRANSMEMBRANE DOMAIN
dc.subject
WATER FRUSTRATION
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Protein structural defects enable pharmaceutical targeting while functionalizing the M2 proton channel
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-12-18T19:33:50Z
dc.journal.volume
514
dc.journal.number
1
dc.journal.pagination
86-91
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina. AF Innovation Pharma Consultancy GmbH; Argentina. Collegium Basilea; Suiza
dc.journal.title
Biochemical and Biophysical Research Communications
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bbrc.2019.04.094
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0006291X19307363
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