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dc.contributor.author
Valsecchi, Wanda Mariela
dc.contributor.author
Cousido Siah, Alexandra
dc.contributor.author
Defelipe, Lucas Alfredo
dc.contributor.author
Mitschler, André
dc.contributor.author
Podjarny, Alberto Daniel
dc.contributor.author
Santos, Javier
dc.contributor.author
Delfino, Jose Maria
dc.date.available
2018-03-28T18:44:35Z
dc.date.issued
2016-06
dc.identifier.citation
Valsecchi, Wanda Mariela; Cousido Siah, Alexandra; Defelipe, Lucas Alfredo; Mitschler, André; Podjarny, Alberto Daniel; et al.; The role of the C-terminal region on the oligomeric state and enzymatic activity of Trypanosoma cruzi hypoxanthine phosphoribosyl transferase; Elsevier Science; Biochimica Et Biophysica Acta-proteins And Proteomics; 1864; 6; 6-2016; 655-666
dc.identifier.issn
1570-9639
dc.identifier.uri
http://hdl.handle.net/11336/40443
dc.description.abstract
Hypoxanthine phosphoribosyl transferase from Trypanosoma cruzi (TcHPRT) is a critical enzyme for the survival of the parasite. This work demonstrates that the full-length form in solution adopts a stable and enzymatically active tetrameric form, exhibiting large inter-subunit surfaces. Although this protein irreversibly aggregates during unfolding, oligomerization is reversible and can be modulated by low concentrations of urea. When the C-terminal region, which is predicted as a disordered stretch, is excised by proteolysis, TcHPRT adopts a dimeric state, suggesting that the C-terminal region acts as a main guide for the quaternary arrangement. These results are in agreement with X-ray crystallographic data presented in this work. On the other hand, the C-terminal region exhibits a modulatory role on the enzyme, as attested by the enhanced activity observed for the dimeric form. Bisphosphonates act as substrate-mimetics, uncovering long-range communications among the active sites. All in all, this work contributes to establish new ways applicable to the design of novel inhibitors that could eventually result in new drugs against parasitic diseases.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Bisphosphonates
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Disorder C-Terminal Region
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Enzymatic Activity Modulation
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Proteolysis
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Quaternary Structure
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Reversible Oligomerization
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Stability
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
The role of the C-terminal region on the oligomeric state and enzymatic activity of Trypanosoma cruzi hypoxanthine phosphoribosyl transferase
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-27T20:28:37Z
dc.journal.volume
1864
dc.journal.number
6
dc.journal.pagination
655-666
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Valsecchi, Wanda Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
dc.description.fil
Fil: Cousido Siah, Alexandra. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; Francia. Inserm; Francia
dc.description.fil
Fil: Defelipe, Lucas Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Mitschler, André. Université de Strasbourg; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Podjarny, Alberto Daniel. Centre National de la Recherche Scientifique; Francia. Inserm; Francia. Université de Strasbourg; Francia
dc.description.fil
Fil: Santos, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
dc.description.fil
Fil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
dc.journal.title
Biochimica Et Biophysica Acta-proteins And Proteomics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bbapap.2016.03.005
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1570963916300413
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