Estudio bioquímico y estructural de sistemas de dos componentes involucrados en la adaptación de Brucella abortus a bajas concentraciones de oxígeno

Brucella abortusis a pathogenic bacterium that infects cattle and humans, causing a disease called Brucellosi. This bacterium has an extraordinary metabolic versatility, which allows overcoming the harsh conditions found along the infection cycle, among which the low oxygen tension found in the repl...

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Autor principal: Fernández, Ignacio
Otros Autores: Carrica, Mariela del Carmen
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2017
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2007
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2007.dir/2007.PDF
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Sumario:Brucella abortusis a pathogenic bacterium that infects cattle and humans, causing a disease called Brucellosi. This bacterium has an extraordinary metabolic versatility, which allows overcoming the harsh conditions found along the infection cycle, among which the low oxygen tension found in the replicative niche that Brucella establishes inside its host cell must be highlighted. It has been described that a two-component system formed by the histidine kinase NtrY and the response regulator NtrX participates in the adaptive response of B. abortus to microaerobiosis.\nGiven that there not much is known on how the system works, the main goal of this thesis has been to elucidate the molecular basis of the activation mechanism of the signaling pathway formed by NtrY and NtrX from B. abortus. To fulfill this aim, a biochemical and structural characterization of the NtrY/NtrX system was carried out. It was demonstrated that NtrY is a bifunctional enzyme (kinase and phosphatase), and the relevance of a cysteine residue (C569) on NtrYin vitro regulation in response to redox state was proved. Also, the first structures of NtrX receiver domain and full-length protein were reported, as well as a description of its oligomeric state, its ability to bind ligand and to interact with DNA. The obtained results are an important contribution to the general knowledge of this signaling pathway and provide background to continue investigating the details of the activation mechanism.