Biomimetic dinitrosyl iron complexes: formation and S-nitrosation capability

• Grant number: 17/02728-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: June 01, 2017
• End date: May 31, 2018
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ohara Augusto
• Grantee: Daniela Ramos Truzzi
• Supervisor: Peter C. Ford
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, Santa Barbara (UC Santa Barbara), United States
• Associated to the scholarship: 14/09518-5 - Protein mechanisms of S-nitrosation: kinetics, mechanism and biological implications, BP.PD

Abstract

High molecular weight dinitrosyl iron complexes (DNICs) have been consistently detected in cell and tissues in situations of nitric oxide overproduction since 1965. Despite this fact, the structures of biological DNICs remain unknown whereas the reactivity of synthetic DNICs received limited attention in the literature. Biological DNICs have been proposed to act as nitric oxide reservoirs and carriers. In addition, these complexes have been suggested to play a substantial role in protein S-nitrosation based on experiments with different cell lines. DNIC-mediated S-nitrosation, however, received limited mechanistic and kinetic studies. Our previous study showed that DNIC-GSH does not promote human peroxiredoxin 1 (Prx1) nitrosation. Instead, the thiol protein displaces GSH to produce the high molecular weight DNIC-Prx. In addition, our preliminary data suggested that monodentate proteins are unlikely to be the preferential ligands for cellular DNIC because they are displaced by bidentate proteins. In contrast, bidentate protein-bound DNICs are not displaced by monodentate ones in the time range of hours. In this project, peptides that mimic the active site of important thiol redox enzymes will be employed to investigate the kinetics and the mechanisms of bidentate peptide-bond DNIC formation and reactivity. The data from these simple model peptides can provide new insights into the possible target proteins that compose biological DNIC. It is also our aim to explore the possibility of bidentate peptide-bond DNIC promote S-nitrosation reaction. (AU)

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)

TRUZZI, DANIELA R.; AUGUSTO, OHARA; FORD, PETER C.. Thiyl radicals are co-products of dinitrosyl iron complex (DNIC) formation. CHEMICAL COMMUNICATIONS, v. 55, n. 62, p. 9156-9159, AUG 11 2019. (13/07937-8, 17/02728-2, 14/09518-5)

TRUZZI, DANIELA R.; AUGUSTO, OHARA; IRETSKII, ALEXEI V.; FORD, PETER C.. Dynamics of Dinitrosyl Iron Complex (DNIC) Formation with Low Molecular Weight Thiols. Inorganic Chemistry, v. 58, n. 19, p. 13446-13456, OCT 7 2019. (17/02728-2, 13/07937-8, 14/09518-5)