Title: Nitric Oxide Interacting with Glutathione Transferases
Authors: Lo Bello, M
Parker, LJ
Parker, MW
Ricci, G
Issue Year: 2018
Publisher ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
Series :
Abstract This short review deals with nitric oxide interacting with proteins (e.g., glutathione transferases) in the presence of GSH and iron. GST P1-1 may act as a NO carrier protein when GSH depletion occurs in the cell. Conversely, in the presence of GSH and traces of ferrous ions, the new formed dinitrosyl-diglutathionyl-iron complexes (DNDGICs) may act as activity modulators with GST P1-1 through competitive inhibition and as strong oxidants with glutathione reductase through irreversible inhibition. DNICs formation inside the cell is followed by a strong interaction with a number of proteins including GSTs and has been object of a number of papers where the most recently evolved GSTs bind DNICs at the active site with the extraordinary affinity. Crystallographic studies of GST P1-1 in complex with DNICs have shown that the active site Tyr-7 coordinates to the iron atom through its phenolate group by displacing one of the GSH ligands. Despite the high binding affinity for this complex and the presence of GST P1-1 in bacteria in large amounts, the disappearance of the complex is clearly dependent on iron availability. In other cells, the same complex present at a cytosolic concentration of 0.19 mM, as strongly bound to alpha-class GSTs, exerts full protection of glutathione reductase activity from NO where it might act as irreversible inhibitor. Thus, we suggest that specific sequestering of DNDGIC is a physiological protective mechanism when cells are exposed to excessive levels of nitric oxide. In this case, other studies have assessed the role of GST P1-1 (as long-term storage of DNICs) and the role of MRP1 in the transport of DNICs outside the cell. It appears that both proteins exert through an opposite but combined effect a great protection from the cytotoxic effects of NO.
URI: https://publications.svi.edu.au/publications/4689
ISSN
Other Identifiers 10.1016/B978-0-12-811020-1.00012-0
Publication type Article