Title
Electrochemical evidence for neuroglobin activity on NO at physiological concentrations Electrochemical evidence for neuroglobin activity on NO at physiological concentrations
Author
Faculty/Department
Faculty of Sciences. Chemistry
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Chemistry
Biology
Human medicine
Source (journal)
Journal of biological chemistry. - Baltimore, Md
Volume/pages
291(2016) :36 , p. 18959-18966
ISSN
0021-9258
ISI
000383242300031
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The true function of neuroglobin (Ngb) and, particularly, human Ngb (NGB) has been under debate since its discovery 15 years ago. It has been expected to play a role in oxygen binding/supply, but a variety of other functions have been put forward, including NO dioxygenase activity. However, in vitro studies that could unravel these potential roles have been hampered by the lack of an Ngb-specific reductase. In this work, we used electrochemical measurements to investigate the role of an intermittent internal disulfide bridge in determining NO oxidation kinetics at physiological NO concentrations. The use of a polarized electrode to efficiently interconvert the ferric (Fe3+) and ferrous (Fe2+) forms of an immobilized NGB showed that the disulfide bridge both defines the kinetics of NO dioxygenase activity and regulates appearance of the free ferrous deoxy-NGB, which is the redox active form of the protein in contrast to oxy-NGB. Our studies further identified a role for the distal histidine, interacting with the hexacoordinated iron atom of the heme, in oxidation kinetics. These findings may be relevant in vivo, for example in blocking apoptosis by reduction of ferric cytochrome c, and gentle tuning of NO concentration in the tissues.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/1e98e1/134340.pdf
Handle