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dc.contributor.author
Balatti, Galo Ezequiel
dc.contributor.author
Barletta Roldan, Patricio German
dc.contributor.author
Parisi, Gustavo Daniel
dc.contributor.author
Tosatto, Silvio. C. E.
dc.contributor.author
Bellanda, Massimo
dc.contributor.author
Fernández Alberti, Sebastián
dc.date.available
2022-08-31T15:59:09Z
dc.date.issued
2021-12
dc.identifier.citation
Balatti, Galo Ezequiel; Barletta Roldan, Patricio German; Parisi, Gustavo Daniel; Tosatto, Silvio. C. E.; Bellanda, Massimo; et al.; Intrinsically Disordered Region Modulates Ligand Binding in Glutaredoxin 1 from Trypanosoma Brucei; American Chemical Society; Journal of Physical Chemistry B; 125; 49; 12-2021; 13366-13375
dc.identifier.issn
1520-6106
dc.identifier.uri
http://hdl.handle.net/11336/167046
dc.description.abstract
Glutaredoxins are small proteins that share a common well-conserved thioredoxin-fold and participate in a wide variety of biological processes. Among them, class II Grx are redox-inactive proteins involved in iron–sulfur (Fe-S) metabolism. In the present work, we report different structural and dynamics aspects of 1CGrx1 from the pathogenic parasite Trypanosoma brucei that differentiate it from other orthologues by the presence of a parasite-specific unstructured N-terminal extension whose role has not been fully elucidated yet. Previous nuclear magnetic resonance (NMR) studies revealed significant differences with respect to the mutant lacking the disordered tail. Herein, we have performed atomistic molecular dynamics simulations that, complementary to NMR studies, confirm the intrinsically disordered nature of the N-terminal extension. Moreover, we confirm the main role of these residues in modulating the conformational dynamics of the glutathione-binding pocket. We observe that the N-terminal extension modifies the ligand cavity stiffening it by specific interactions that ultimately modulate its intrinsic flexibility, which may modify its role in the storage and/or transfer of preformed iron–sulfur clusters. These unique structural and dynamics aspects of Trypanosoma brucei 1CGrx1 differentiate it from other orthologues and could have functional relevance. In this way, our results encourage the study of other similar protein folding families with intrinsically disordered regions whose functional roles are still unrevealed and the screening of potential 1CGrx1 inhibitors as antitrypanosomal drug candidates.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
PROTEIN
dc.subject
GLUTAREDOXIN
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MOLECULAR
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DYNAMICS
dc.subject.classification
Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Intrinsically Disordered Region Modulates Ligand Binding in Glutaredoxin 1 from Trypanosoma Brucei
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-08-29T13:30:25Z
dc.identifier.eissn
1520-5207
dc.journal.volume
125
dc.journal.number
49
dc.journal.pagination
13366-13375
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Balatti, Galo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
dc.description.fil
Fil: Barletta Roldan, Patricio German. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
dc.description.fil
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
dc.description.fil
Fil: Tosatto, Silvio. C. E.. Università di Padova; Italia
dc.description.fil
Fil: Bellanda, Massimo. Università di Padova; Italia
dc.description.fil
Fil: Fernández Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
dc.journal.title
Journal of Physical Chemistry B
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.jpcb.1c07035
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/acs.jpcb.1c07035
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