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

• Grant number: 13/10780-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2013
• End date: October 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Ohara Augusto
• Grantee: Robert Ryan Geyer
• Host 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.

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, APR 2018. (13/11364-3, 13/23087-4, 13/10780-3)