title: Electrochemical Evidence for Neuroglobin Activity on NO at Physiological Concentrations.
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 (Fe(3+)) and ferrous (Fe(2+)) 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.
authors.affiliation: From the Departments of Chemistry and.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Trashin
authors.affiliation: From the Departments of Chemistry and.
authors.forename: Mats
authors.initials: M
authors.lastname: de Jong
authors.affiliation: Biomedical Sciences, University of Antwerp, 2010 Antwerp, Belgium.
authors.forename: Evi
authors.initials: E
authors.lastname: Luyckx
authors.affiliation: Biomedical Sciences, University of Antwerp, 2010 Antwerp, Belgium.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
authors.affiliation: From the Departments of Chemistry and karolien.dewael@uantwerpen.be.
authors.forename: Karolien
authors.initials: K
authors.lastname: De Wael
mesh_terms: D055664:Electrochemical Techniques; D004566:Electrodes; D005914:Globins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D000078787:Neuroglobin; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D009569:Nitric Oxide; D005914:Globins; D010105:Oxygenases; C114415:nitric oxide dioxygenase
keywords: electrochemistry; electron transfer; neuroglobin; nitric oxide; oxygen binding; protein chemistry