Universidad Peruana Cayetano Heredia

Mycobacterium tuberculosis ribosomal protein S1 (RpsA) and variants with truncated C-terminal end show absence of interaction with pyrazinoic acid

Mostrar el registro sencillo del ítem

dc.contributor.author Vallejos-Sánchez, K.
dc.contributor.author Lopez, J.M.
dc.contributor.author Antiparra, R.
dc.contributor.author Toscano, E.
dc.contributor.author Saavedra Pastor, Herbert
dc.contributor.author Kirwan, D.E.
dc.contributor.author Amzel, L.M.
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Maruenda, H.
dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.date.accessioned 2020-12-14T16:10:22Z
dc.date.available 2020-12-14T16:10:22Z
dc.date.issued 2020
dc.identifier.uri https://hdl.handle.net/20.500.12866/8838
dc.description.abstract Pyrazinamide (PZA) is an antibiotic used in first- and second-line tuberculosis treatment regimens. Approximately 50% of multidrug-resistant tuberculosis and over 90% of extensively drug-resistant tuberculosis strains are also PZA resistant. Despite the key role played by PZA, its mechanisms of action are not yet fully understood. It has been postulated that pyrazinoic acid (POA), the hydrolyzed product of PZA, could inhibit trans-translation by binding to Ribosomal protein S1 (RpsA) and competing with tmRNA, the natural cofactor of RpsA. Subsequent data, however, indicate that these early findings resulted from experimental artifact. Hence, in this study we assess the capacity of POA to compete with tmRNA for RpsA. We evaluated RpsA wild type (WT), RpsA ∆A438, and RpsA ∆A438 variants with truncations towards the carboxy terminal end. Interactions were measured using Nuclear Magnetic Resonance spectroscopy (NMR), Isothermal Titration Calorimetry (ITC), Microscale Thermophoresis (MST), and Electrophoretic Mobility Shift Assay (EMSA). We found no measurable binding between POA and RpsA (WT or variants). This suggests that RpsA may not be involved in the mechanism of action of PZA in Mycobacterium tuberculosis, as previously thought. Interactions observed between tmRNA and RpsA WT, RpsA ∆A438, and each of the truncated variants of RpsA ∆A438, are reported. en_US
dc.language.iso eng
dc.publisher Springer Nature
dc.relation.ispartofseries Scientific Reports
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Biophysics en_US
dc.subject Molecular biology en_US
dc.title Mycobacterium tuberculosis ribosomal protein S1 (RpsA) and variants with truncated C-terminal end show absence of interaction with pyrazinoic acid en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1038/s41598-020-65173-z
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.07
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.relation.issn 2045-2322


Ficheros en el ítem

Ficheros Tamaño Formato Ver

No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

info:eu-repo/semantics/restrictedAccess Excepto si se señala otra cosa, la licencia del ítem se describe como info:eu-repo/semantics/restrictedAccess

Buscar en el Repositorio


Listar

Panel de Control

Estadísticas