Structure, nitric oxide (NO) generation and antitumor activity of binuclear tetranitrosyl iron complex with 4-aminothiophenolyl as nitrosyl ferredoxins mimic

Nitric oxide (NO) is a highly reactive water-soluble gas encountered by bacteria endogenously as an intermediate of denitrification and exogenously as one of the radical species deployed by macrophages against invading pathogens. Bacteria therefore require a mechanism to detoxify NO. Escherichia coli flavorubredoxin and its associated oxidoreductase, encoded by the norV and norW genes respectively, reduces NO to nitrous oxide under anaerobic conditions. Transcription of the norVW genes is activated in response to NO by the σ54-dependent regulator NorR, a member of the prokaryotic enhancer binding protein family. NorR binds co-operatively to three enhancer sites to regulate transcription of both norVW and the divergently transcribed norR gene. In the present paper, we show that disruption of any one of the three GT-(N7)-AC NorR binding sites in the norR–norVW intergenic region prevents both activation of norVW expression and autogenous repression of the norR promoter by NorR. We have recently demonstrated that the N-terminal GAF (cGMP-specific and -stimulated phosphodiesterases, Anabaena adenylate cyclases and Escherichia coli FhlA) domain of NorR contains a non-haem mononuclear iron centre and senses NO by formation of a mono-nitrosyl iron complex. Site-directed mutagenesis has identified candidate protein ligands to the ferrous iron centre in the GAF domain.

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The antitumor activity of the S-nitrosoglutathione and dinitrosyl iron complex with glutathione: Comparative studies

BIOPHYSICS ◽

10.1134/s0006350915060263 ◽

2015 ◽

Vol 60 (6) ◽

pp. 963-969 ◽

Cited By ~ 6

Author(s):

A. F. Vanin ◽

L. A. Ostrovskaya ◽

D. B. Korman ◽

L. N. Kubrina ◽

R. R. Borodulin ◽

...

Keyword(s):

Antitumor Activity ◽

Comparative Studies ◽

Iron Complex ◽

Dinitrosyl Iron Complex ◽

Dinitrosyl Iron

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NITRIC OXIDE (NO)-CHEMOTHERAPY OF GLIOMAS: EXPERIMENTAL IN VITRO AND IN VIVO STUDIES OF MECHANISMS OF ANTITUMOR ACTIVITY OF LOWMOLECULAR-WEIGHT DINITROSYL IRON COMPLEXES

10.19163/medchemrussia2021-2021-114 ◽

2021 ◽

Author(s):

N.A. Sanina ◽

Keyword(s):

Nitric Oxide ◽

Antitumor Activity ◽

Iron Complexes ◽

Dinitrosyl Iron Complexes ◽

In Vivo Studies ◽

Dinitrosyl Iron

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The Relationship of Glutathione-S-Transferase and Multi-Drug Resistance-Related Protein 1 in Nitric Oxide (NO) Transport and Storage

Molecules ◽

10.3390/molecules26195784 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5784

Author(s):

Tiffany M. Russell ◽

Mahan Gholam Azad ◽

Des R. Richardson

Keyword(s):

Nitric Oxide ◽

Drug Resistance ◽

Ammonia Oxidation ◽

Iron Complexes ◽

Physiological Model ◽

Iron Complex ◽

Multi Drug Resistance ◽

Related Protein ◽

Glutathione S Transferase ◽

And Storage

Nitric oxide is a diatomic gas that has traditionally been viewed, particularly in the context of chemical fields, as a toxic, pungent gas that is the product of ammonia oxidation. However, nitric oxide has been associated with many biological roles including cell signaling, macrophage cytotoxicity, and vasodilation. More recently, a model for nitric oxide trafficking has been proposed where nitric oxide is regulated in the form of dinitrosyl-dithiol-iron-complexes, which are much less toxic and have a significantly greater half-life than free nitric oxide. Our laboratory has previously examined this hypothesis in tumor cells and has demonstrated that dinitrosyl-dithiol-iron-complexes are transported and stored by multi-drug resistance-related protein 1 and glutathione-S-transferase P1. A crystal structure of a dinitrosyl-dithiol-iron complex with glutathione-S-transferase P1 has been solved that demonstrates that a tyrosine residue in glutathione-S-transferase P1 is responsible for binding dinitrosyl-dithiol-iron-complexes. Considering the roles of nitric oxide in vasodilation and many other processes, a physiological model of nitric oxide transport and storage would be valuable in understanding nitric oxide physiology and pathophysiology.

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