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The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols

Miller, T. W.; Cherney, M. M.; Lee, A. J.; Francoleon, N. E.; Farmer, P. J.; King, S. B.; Hobbs, A. J.; ... Fukuto, J. M.; + view all (2009) The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols. Journal of Biological Chemistry , 284 (33) pp. 21788-21796. 10.1074/jbc.M109.014282. Green open access

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Abstract

It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme. Like NO, HNO activation appears to occur via interaction with the regulatory ferrous heme on sGC. Somewhat unexpectedly, HNO does not activate the ferric form of the enzyme. Finally, HNO-mediated cysteine thiol modification appears to also affect enzyme activity leading to inhibition. Thus, sGC activity can be regulated by HNO via interactions at both the regulatory heme and cysteine thiols.

Type: Article
Title: The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/jbc.M109.014282
Publisher version: http://dx.doi.org/10.1074/jbc.M109.014282
Language: English
Additional information: This research was originally published in the Journal of Biological Chemistry. Miller, T. W. and Cherney, M. M. and Lee, A. J. and Francoleon, N. E. and Farmer, P. J. and King, S. B. and Hobbs, A. J. and Miranda, K. M. and Burstyn, J. N. and Fukuto, J. M. The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols. Journal of Biological Chemistry. 2009 284 (33). pp. 21788-21796. © the American Society for Biochemistry and Molecular Biology. Reproduced here under terms of Author's Choice. Creative Commons Attribution Non-Commercial License applies to Author Choice Articles, please see http://creativecommons.org/licenses/by-nc/3.0/
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/20042
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