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

Heme 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-ir...

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Autores principales: Soldano, Anabel, Klinke, Sebastián, Otero, Lisandro H., Rivera, Mario, Catalano-Dupuy, Daniela L., Ceccarelli, Eduardo Augusto
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: Public Library of Science (PLOS) 2021
Materias:
Leptospira interrogans
Virulence Factors
Heme Oxygenase (Decyclizing)
Catalytic Mechanisms
Acceso en línea:http://hdl.handle.net/2133/19676
http://hdl.handle.net/2133/19676
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-19676
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
topic Leptospira interrogans
Virulence Factors
Heme Oxygenase (Decyclizing)
Catalytic Mechanisms
spellingShingle Leptospira interrogans
Virulence Factors
Heme Oxygenase (Decyclizing)
Catalytic Mechanisms
Soldano, Anabel
Klinke, Sebastián
Otero, Lisandro H.
Rivera, Mario
Catalano-Dupuy, Daniela L.
Ceccarelli, Eduardo Augusto
Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism
topic_facet Leptospira interrogans
Virulence Factors
Heme Oxygenase (Decyclizing)
Catalytic Mechanisms
description Heme 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.
format article
artículo
publishedVersion
author Soldano, Anabel
Klinke, Sebastián
Otero, Lisandro H.
Rivera, Mario
Catalano-Dupuy, Daniela L.
Ceccarelli, Eduardo Augusto
author_facet Soldano, Anabel
Klinke, Sebastián
Otero, Lisandro H.
Rivera, Mario
Catalano-Dupuy, Daniela L.
Ceccarelli, Eduardo Augusto
author_sort Soldano, Anabel
title Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism
title_short Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism
title_full Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism
title_fullStr Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism
title_full_unstemmed Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism
title_sort structural and mutational analyses of the leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism
publisher Public Library of Science (PLOS)
publishDate 2021
url http://hdl.handle.net/2133/19676
http://hdl.handle.net/2133/19676
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