Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism

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dc.citation.titlePLOS ONEes
dc.citation.volume12(8)es
dc.creatorSoldano, Anabel
dc.creatorKlinke, Sebastián
dc.creatorOtero, Lisandro H.
dc.creatorRivera, Mario
dc.creatorCatalano-Dupuy, Daniela L.
dc.creatorCeccarelli, Eduardo Augusto
dc.date.accessioned2021-02-23T19:20:24Z
dc.date.available2021-02-23T19:20:24Z
dc.date.issued2017-08-03
dc.descriptionHeme oxygenase from Leptospira interrogans is an important virulence factor. During catalysis, redox equivalents are provided to this enzyme by the plastidic-type ferredoxin-NADP+ reductase also found in L. interrogans. This process may have evolved to aid this bacterial pathogen to obtain heme-iron from their host and enable successful colonization. Herein we report the crystal structure of the heme oxygenase-heme complex at 1.73 Å resolution. The structure reveals several distinctive features related to its function. A hydrogen bonded network of structural water molecules that extends from the catalytic site to the protein surface was cleared observed. A depression on the surface appears to be the H+ network entrance from the aqueous environment to the catalytic site for O2 activation, a key step in the heme oxygenase reaction. We have performed a mutational analysis of the F157, located at the above-mentioned depression. The mutant enzymes were unable to carry out the complete degradation of heme to biliverdin since the reaction was arrested at the verdoheme stage. We also observed that the stability of the oxyferrous complex, the efficiency of heme hydroxylation and the subsequent conversion to verdoheme was adversely affected. These findings underscore a long-range communication between the outer fringes of the hydrogenbonded network of structural waters and the heme active site during catalysis. Finally, by analyzing the crystal structures of ferredoxin-NADP+ reductase and heme oxygenase, we propose a model for the productive association of these proteins.es
dc.descriptionPara citar este articulo: Soldano A, Klinke S, Otero LH, Rivera M, Catalano-Dupuy DL, Ceccarelli EA (2017) Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism. PLoS ONE 12(8): e0182535. https://doi.org/10.1371/ journal.pone.0182535
dc.description.filFil: Soldano, Anabel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Klinke, Sebastián. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBA-CONICET); Argentina.es
dc.description.filFil: Klinke, Sebastián. Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM); Argentina.es
dc.description.filFil: Otero, Lisandro H. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBA-CONICET); Argentina.es
dc.description.filFil: Otero, Lisandro H. Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM); Argentina.es
dc.description.filFil: Rivera, Mario. University of Kansas. Adams Institute for Bioanalytical Chemistry. Department of Chemistry; United States.es
dc.description.filFil: Catalano-Dupuy, Daniela L. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Ceccarelli, Eduardo A. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT-2012-1841es
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PIP 0345es
dc.formatapplication/pdf
dc.format.extent1-22es
dc.identifier.issn1932-6203es
dc.identifier.urihttp://hdl.handle.net/2133/19676
dc.language.isoenges
dc.publisherPublic Library of Science (PLOS)es
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0182535es
dc.relation.publisherversionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182535es
dc.rightsopenAccesses
dc.rights.holderUniversidad Nacional de Rosarioes
dc.rights.holderSoldano, Anabeles
dc.rights.holderKlinke, Sebastiánes
dc.rights.holderOtero, Lisandro H.es
dc.rights.holderRivera, Marioes
dc.rights.holderCatalano-Dupuy, Daniela L.es
dc.rights.holderCeccarelli, Eduardo A.es
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectLeptospira interroganses
dc.subjectVirulence Factorses
dc.subjectHeme Oxygenase (Decyclizing)es
dc.subjectCatalytic Mechanismses
dc.titleStructural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanismes
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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