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Oxidation and aggregation of human superoxide dismutase 1 resulting from its bicarbonate-dependent peroxidase activity

Grant number: 13/10780-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2013
Effective date (End): October 31, 2016
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal researcher:Ohara Augusto
Grantee:Robert Ryan Geyer
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:08/57721-3 - Redoxome, AP.TEM

Abstract

The cytosolic enzyme Cu,Zn-superoxide dismutase (SOD1) is an intriguing enzyme. It is one of the most important antioxidant defenses but can also present pro-oxidant activities, such as the bicarbonate-dependent peroxidase activity. On the other hand, the human enzyme (hSOD1) is a small protein (153 amino acids and 1 copper and 1 zinc ion per monomer), which in the native state is a remarkably stable non covalent homodimer highly resistant to detergents and proteolysis. Nevertheless, point mutations of hSOD1 (>150 have been described) are associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) (http://alsod.iop.kcl.ac.uk/). As is the case of other neurodegenerative diseases, protein misfolding and aggregation is a hallmark of ALS. Yet, the precise mechanism of SOD1 aggregation is currently unknown. Previous work by our group and others has raised the possibility that the bicarbonate-dependent peroxidase activity of human SOD1 (hSOD1) could result in the oxidation and aggregation of hSOD1. The goal of this project is to characterize the initial steps of hSOD1 aggregation-likely as a result of protein unfolding/misfolding-upon oxidation during the bicarbonate-dependent peroxidase activity.

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Scientific publications
(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)
KABUTOMORI, JESSICA; BELOTO-SILVA, OLIVIA; GEYER, R. RYAN; MUSA-AZIZ, RAIF. Lithobates catesbeianus (American Bullfrog) oocytes: a novel heterologous expression system for aquaporins. BIOLOGY OPEN, v. 7, n. 4, . (13/11364-3, 13/23087-4, 13/10780-3)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.