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Role of metal ions on the activity of Mycobacterium tuberculosis pyrazinamidase

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dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Ferrer, P.
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Christiansen, G.
dc.contributor.author Moreno-Román, P.
dc.contributor.author Gutiérrez, A.H.
dc.contributor.author Sotelo, J.
dc.contributor.author Evangelista, W.
dc.contributor.author Fuentes, P.
dc.contributor.author Rueda, D.
dc.contributor.author Flores, M.
dc.contributor.author Olivera, P.
dc.contributor.author Solis, J.
dc.contributor.author Pesaresi, A.
dc.contributor.author Lamba, D.
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.date.accessioned 2022-01-18T19:35:51Z
dc.date.available 2022-01-18T19:35:51Z
dc.date.issued 2012
dc.identifier.uri https://hdl.handle.net/20.500.12866/11215
dc.description.abstract Pyrazinamidase of Mycobacterium tuberculosis catalyzes the conversion of pyrazinamide to the active molecule pyrazinoic acid. Reduction of pyrazinamidase activity results in a level of pyrazinamide resistance. Previous studies have suggested that pyrazinamidase has a metal-binding site and that a divalent metal cofactor is required for activity. To determine the effect of divalent metals on the pyrazinamidase, the recombinant wild-type pyrazinamidase corresponding to the H37Rv pyrazinamide-susceptible reference strain was expressed in Escherichia coli with and without a carboxy terminal. His-tagged pyrazinamidase was inactivated by metal depletion and reactivated by titration with divalent metals. Although Co2+, Mn2+, and Zn2+ restored pyrazinamidase activity, only Co2+ enhanced the enzymatic activity to levels higher than the wild-type pyrazinamidase. Cu2+, Fe 2+, Fe3+, and Mg2+ did not restore the activity under the conditions tested. Various recombinant mutated pyrazinamidases with appropriate folding but different enzymatic activities showed a differential pattern of recovered activity. X-ray fluorescence and atomic absorbance spectroscopy showed that recombinant wild-type pyrazinamidase expressed in E. coli most likely contained Zn. In conclusion, this study suggests that M. tuberculosis pyrazinamidase is a metalloenzyme that is able to coordinate several ions, but in vivo, it is more likely to coordinate Zn2+. However, in vitro, the metal-depleted enzyme could be reactivated by several divalent metals with higher efficiency than Zn. en_US
dc.language.iso eng
dc.publisher American Society of Tropical Medicine and Hygiene
dc.relation.ispartofseries American Journal of Tropical Medicine and Hygiene
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Controlled study en_US
dc.subject in vitro study en_US
dc.subject in vivo study en_US
dc.subject non protein expression en_US
dc.subject unclassified drug en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject Kinetics en_US
dc.subject pyrazinamide en_US
dc.subject Amidohydrolases en_US
dc.subject atomic absorption spectrometry en_US
dc.subject bacterial enzyme en_US
dc.subject carboxy terminal sequence en_US
dc.subject Circular Dichroism en_US
dc.subject cobalt en_US
dc.subject divalent cation en_US
dc.subject enzyme activity en_US
dc.subject enzyme inactivation en_US
dc.subject enzyme reactivation en_US
dc.subject Escherichia coli en_US
dc.subject ferric ion en_US
dc.subject ferrous ion en_US
dc.subject magnesium ion en_US
dc.subject manganese en_US
dc.subject metal ion en_US
dc.subject Metals en_US
dc.subject Models, Molecular en_US
dc.subject pyrazinamidase en_US
dc.subject recombinant enzyme en_US
dc.subject Spectrophotometry, Atomic en_US
dc.subject titrimetry en_US
dc.subject wild type en_US
dc.subject X ray fluorescence en_US
dc.subject zinc ion en_US
dc.title Role of metal ions on the activity of Mycobacterium tuberculosis pyrazinamidase en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.4269/ajtmh.2012.10-0565
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.06
dc.relation.issn 1476-1645


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