Biological aspects of thiols: protein structure, antioxidant defense, cell signaling and redox states

• Grant number: 07/58147-6
• Support Opportunities: Research Projects - Thematic Grants
• Start date: April 01, 2008
• End date: March 31, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Luis Eduardo Soares Netto
• Grantee: Luis Eduardo Soares Netto
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 10/51966-4 - Regulation and role of Ohr/OhrR antioxidant defense system in the physiology and pathogenicity of Chromobacterium violaceum, BP.PD; 08/08761-2 - Investigation of the involvement of oxidative stress in animal models of muscular dystrophy, BP.MS; 08/07971-3 - Kinetic characterization and search for inhibitors of Ohr (Organic Hydroperoxide Resistance Protein) from Xylella fastidiosa, BP.MS

Abstract

The classical concept of oxidative stress is "a disturbance in the pro-oxidant-antioxidant balance in favor of the former". However, the accumulation of data indicates that a more useful definition is a "disruption of redox signaling and control" [...]. The tri-peptide glutathione plays a central role in the redox homeostasis, but there are also other thiols that participate in redox signaling. These thiols that make part of redox pairs (RSH/RSSR) are enzymes that contain reactive cysteines (such as thioredoxins, glutaredoxins and peroxiredoxins) and are widely distributed. In this project, we propose to characterize structurally and functionally several thiol systems, especially those derived from the model organism, Saccharomyces cerevisiae. We have already elucidated the structures of several proteins that compose these systems and now o intend: 1) to elucidate novel structures; 2) continue to make functional-structural correlations and 3) determined structure of protein complexes. Among these studies, we intend to investigate in further details a new antioxidant pathway: the reduction of 1-Cys peroxiredoxins by ascorbate (vitamin C). Our studies [...] changed the "thiols specific antioxidant paradigm" of these thiol-disulfide oxido¬reductases and opened the perspective that these low molecular weight compounds can interfere in the redox states of several thiol systems and, consequently, in redox signaling. We also intend to continue our characterization of antioxidant systems from Xylella fastidiosa. Previously, we elucidated the first structure of a protein (Ohr) from Xylella fastidiosa [...]. Since Ohr is exclusively present in bacteria, this protein may represent a promising target for drug design. Other antioxidant systems from Xylella fastidiosa are also currently being analyzed. (AU)

Scientific publications

(7)

(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)

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. (07/58147-6, 12/21722-1, 13/07937-8)

CUSSIOL, JOSE R. R.; ALEGRIA, THIAGO G. P.; SZWEDA, LUKE I.; NETTO, LUIS E. S.. Ohr (Organic Hydroperoxide Resistance Protein) Possesses a Previously Undescribed Activity, Lipoyl-dependent Peroxidase. Journal of Biological Chemistry, v. 285, n. 29, p. 21943-21950, JUL 16 2010. (07/58147-6)

DA SILVA NETO, JOSE F.; NEGRETTO, CAROLINE C.; NETTO, LUIS E. S.. Analysis of the Organic Hydroperoxide Response of Chromobacterium violaceum Reveals That OhrR Is a Cys-Based Redox Sensor Regulated by Thioredoxin. PLoS One, v. 7, n. 10, OCT 11 2012. (07/58147-6, 08/57721-3)

MALVEZZI, ALBERTO; HIGA, PATRICIA M.; AMARAL, ANTONIA T. -DO; SILVA, GUSTAVO M.; GOZZO, FABIO C.; FERRO, EMER S.; CASTRO, LEANDRO M.; DE REZENDE, LEANDRO; MONTEIRO, GISELE; DEMASI, MARILENE. The Cysteine-Rich Protein Thimet Oligopeptidase as a Model of the Structural Requirements for S-glutathiolation and Oxidative Oligomerization. PLoS One, v. 7, n. 6, JUN 25 2012. (07/58147-6, 08/06731-9)

TAIRUM, CARLOS A.; DE OLIVEIRA, MARCOS A.; HORTA, BRUNO B.; ZARA, FERNANDO J.; NETTO, LUIS E. S.. Disulfide Biochemistry in 2-Cys Peroxiredoxin: Requirement of Glu50 and Arg146 for the Reduction of Yeast Tsa1 by Thioredoxin. Journal of Molecular Biology, v. 424, n. 1-2, p. 28-41, NOV 23 2012. (07/58147-6, 08/57721-3)

SILVA, GUSTAVO M.; NETTO, LUIS E. S.; SIMOES, VANESSA; SANTOS, LUIZ F. A.; GOZZO, FABIO C.; DEMASI, MARCOS A. A.; OLIVEIRA, CRISTIANO L. P.; BICEV, RENATA N.; KLITZKE, CLECIO F.; SOGAYAR, MARI C.; et al. Redox Control of 20S Proteasome Gating. Antioxidants & Redox Signaling, v. 16, n. 11, p. 1183-1194, JUN 2012. (07/58147-6, 08/06731-9)

OLIVEIRA, MARCOS A.; DISCOLA, KAREN F.; ALVES, SIMONE V.; MEDRANO, FRANCISCO J.; GUIMARAES, BEATRIZ G.; NETTO, LUIS E. S.. Insights into the Specificity of Thioredoxin Reductase-Thioredoxin Interactions. A Structural and Functional Investigation of the Yeast Thioredoxin System. BIOCHEMISTRY, v. 49, n. 15, p. 3317-3326, 2010. (07/58147-6)