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Structural and biochemical characterization of Ohr/OsmC family proteins: emphasis on the characterization of a Francisella tularensis protein involved in pathogenicity

Grant number: 12/21722-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2012
Effective date (End): November 30, 2016
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal Investigator:Luis Eduardo Soares Netto
Grantee:Diogo de Abreu Meireles
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID


Ohr (organic hydroperoxide resistance) proteins are pivotal players in bacterial response to organic hydroperoxide insults. Our group showed that the Cys based, thiol-dependent peroxidase activity of Ohr underlies the organic hydroperoxide sensitivity phenotype (Cussiol et al., 2003). Elucitation of Ohr crystallographic structure prompts us to propose a mechanism of catalysis, where the two cysteine residues besides an arginine and a glutamate residues take place (Oliveira et al., 2006). Ohr enzymes belong to a family of proteins named Ohr/OsmC, which are composed by three main subgroups: subgroup I, represented by Ohr, subgroup II, represented by OsmC and subgroup III, represented by YhfA. Although they share low sequence similarity, they display high structural conservation, including the two active site cysteines. The function of OsmC protein is poorly studied and almost nothing is known about YhfA. In the present project, we intend to investigate the distribuction of Ohr/OsmC proteins in distinct taxonomic groups and propose a new classification, since our initial analyses brought out this need. We also intend to structural and biochemically characterize members of protein subgroup YhfA. Finally, the possible role of Ohr on virulence of Pseudomonas aeruginosa will be investigated. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Enzyme helps bacteria defend themselves against oxidants secreted by immune system 

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GOMES, FERNANDO; PALMA, FLAVIO ROMERO; BARROS, MARIO H.; TSUCHIDA, EDUARDO T.; TURANO, HELENA G.; ALEGRIA, THIAGO G. P.; DEMASI, MARILENE; NETTO, LUIS E. S. Proteolytic cleavage by the inner membrane peptidase (IMP) complex or Oct1 peptidase controls the localization of the yeast peroxiredoxin Prx1 to distinct mitochondrial compartments. Journal of Biological Chemistry, v. 292, n. 41, p. 17011-17024, OCT 13 2017. Web of Science Citations: 4.
MEIRELES, A.; DOMINGOS, R. M.; GAIARSA, J. W.; RAGNONI, E. G.; BANNITZ-FERNANDES, R.; DA SILVA NETO, J. F.; DE SOUZA, R. F.; NETTO, L. E. S. Functional and evolutionary characterization of Ohr proteins in eukaryotes reveals many active homologs among pathogenic fungi. REDOX BIOLOGY, v. 12, p. 600-609, AUG 2017. Web of Science Citations: 5.
PREVIATO-MELLO, MARISTELA; MEIRELES, DIOGO DE ABREU; SOARES NETTO, LUIS EDUARDO; DA SILVA NETO, JOSE FREIRE. Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum. Infection and Immunity, v. 85, n. 8 AUG 2017. Web of Science Citations: 7.
ALEGRIA, THIAGO G. P.; MEIRELES, DIOGO A.; CUSSIOL, JOSE R. R.; HUGO, MARTIN; TRUJILLO, MADIA; DE OLIVEIRA, MARCOS ANTONIO; MIYAMOTO, SAYURI; QUEIROZ, RAPHAEL F.; VALADARES, NAPOLEAO FONSECA; GARRATT, RICHARD C.; RADI, RAFAEL; DI MASCIO, PAOLO; AUGUSTO, OHARA; NETTO, LUIS E. S. Ohr plays a central role in bacterial responses against fatty acid hydroperoxides and peroxynitrite. Proceedings of the National Academy of Sciences of the United States of America, v. 114, n. 2, p. E132-E141, JAN 10 2017. Web of Science Citations: 21.
MEIRELES, DIOGO DE ABREU; PIRES ALEGRIA, THIAGO GERONIMO; ALVES, SIMONE VIDIGAL; ROCHA ARANTES, CARLA RANI; SOARES NETTO, LUIS EDUARDO. A 14.7 kDa Protein from Francisella tularensis subsp novicida (Named FTN_1133), Involved in the Response to Oxidative Stress Induced by Organic Peroxides, Is Not Endowed with Thiol-Dependent Peroxidase Activity. PLoS One, v. 9, n. 6 JUN 24 2014. Web of Science Citations: 5.

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