Investigation of the capability of thioredoxin 1 (S. cerevisiae) bind to dinitrosyl iron complexes

• Grant number: 21/03536-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2021
• End date: June 30, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Daniela Ramos Truzzi
• Grantee: Arthur Migliatti Vetorazzi Ferreira de Pinho
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/17483-0 - Dinitrosyl iron complexes (DNICs): formation, reactivity, and implications for the physiopathology of nitric oxide, AP.JP

Abstract

Nitric oxide (NO) participates in several biological functions such as vasodilation, antioxidant action, and neurotransmission. Despite being a radical, in a biological environment, NO reacts specifically with radicals and metals. The reactions between NO and radicals or heme iron centers are well established, while the reactions between NO and non-heme iron centers are less known despite leading to the formation of the main intracellular NO-metabolites: Dinitrosyl Iron complexes (DNICs). Although these complexes have been detected in cells since 1965, the biological processes in which they are involved are still little explored. The biological DNICs contain thiols of low (cysteine and glutathione) or high molecular weight as ligands. Thiol proteins constitute the majority of DNICs ligands, however, their identity is little known. Initial studies on the dynamics of high molecular weight DNICs in aqueous media indicate that proteins that bind to iron through two amino acid residues (in a bidentate manner) are the preferred ligands of DNICs in biological media. Thioredoxin 1 (Trx1) is an antioxidant enzyme that acts in the control of hydrogen peroxide (H2O2) cellular levels and presents in its active site two cysteines separated by only two amino acid residues, thus Trx1 would coordinate to DNICs in a bidentate manner. Also, it is observed that cells exposed to NO show a reduction in H2O2 metabolism. Based on this, this project proposes to investigate the ability of Trx1 to bind to DNICs aiming to help to identify the proteins that constitute the biological DNICs and also explain the reduction of H2O2 cellular metabolism, since the coordination of Trx1 might lead to its inactivation.(AU)