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dc.contributor.author
Giordana, Lucila
dc.contributor.author
Sosa, Máximo Hernán
dc.contributor.author
Leroux, Alejandro Ezequiel
dc.contributor.author
Mendoza Rodas, Elkin F.
dc.contributor.author
Petray, Patricia Beatriz
dc.contributor.author
Nowicki, Cristina
dc.date.available
2018-06-29T17:15:51Z
dc.date.issued
2018-01
dc.identifier.citation
Giordana, Lucila; Sosa, Máximo Hernán; Leroux, Alejandro Ezequiel; Mendoza Rodas, Elkin F.; Petray, Patricia Beatriz; et al.; Molecular and functional characterization of two malic enzymes from Leishmania parasites; Elsevier Science; Molecular and Biochemical Parasitology; 219; 1-2018; 67-76
dc.identifier.issn
0166-6851
dc.identifier.uri
http://hdl.handle.net/11336/50684
dc.description.abstract
Leishmania parasites cause a broad spectrum of clinical manifestations in humans and the available clinical treatments are far from satisfactory. Since these pathogens require large amounts of NADPH to maintain intracellular redox homeostasis, oxidoreductases that catalyze the production of NADPH are considered as potential drug targets against these diseases. In the sequenced genomes of most Leishmania spp. two putative malic enzymes (MEs) with an identity of about 55% have been identified. In this work, the ME from L. major (LmjF24.0770, Lmj_ME-70) and its less similar homolog from L. mexicana (LmxM.24.0761, Lmex_ME-61) were cloned and functionally characterized. Both MEs specifically catalyzed NADPH production, but only Lmex_ME-61 was activated by L-aspartate. Unlike the allosterically activated human ME, Lmex_ME-61 exhibited typical hyperbolic curves without any sign of cooperativity in the absence of L-aspartate. Moreover, Lmex_ME-61 and Lmj_ME-70 differ from higher eukaryotic homologs in that they display dimeric instead of tetrameric molecular organization. Homology modeling analysis showed that Lmex_ME-61 and Lmj_ME-70 notably differ in their surface charge distribution; this feature encompasses the coenzyme binding pockets as well. However, in both isozymes, the residues directly involved in the coenzyme binding exhibited a good degree of conservation. Besides, only Lmex_ME-61 and its closest homologs were immunodetected in cell-free extracts from L. mexicana, L. amazonensis and L. braziliensis promastigotes. Our findings provide a first glimpse into the biochemical properties of leishmanial MEs and suggest that MEs could be potentially related to the metabolic differences among the species of Leishmania parasites.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Leishmania
dc.subject
Malic Enzymes
dc.subject
Nadph Production
dc.subject
Redox Metabolism
dc.subject.classification
Salud Ocupacional
dc.subject.classification
Ciencias de la Salud
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Molecular and functional characterization of two malic enzymes from Leishmania parasites
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-06T13:46:26Z
dc.journal.volume
219
dc.journal.pagination
67-76
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Giordana, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
dc.description.fil
Fil: Sosa, Máximo Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
dc.description.fil
Fil: Leroux, Alejandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.description.fil
Fil: Mendoza Rodas, Elkin F.. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil
dc.description.fil
Fil: Petray, Patricia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
dc.description.fil
Fil: Nowicki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
dc.journal.title
Molecular and Biochemical Parasitology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0166685117301342
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.molbiopara.2017.11.001


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  • Articulos(ININFA) [148]
    Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
  • Articulos(IQUIFIB) [381]
    Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
  • Articulos(IMPAM) [225]
    Articulos de INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
  • Articulos(IBIOBA - MPSP) [139]
    Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK

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