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

Thomas W. Miller, Melisa M. Cherney, Andrea J. Lee, Nestor E. Francolean, Patrick J. Farmer, S. Bruce King, Adrian J. Hobbs, Katrina M. Miranda, Judith N. Burstyn, Jon M. Fukuto

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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.

Original languageEnglish (US)
Pages (from-to)21788-21796
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number33
DOIs
StatePublished - Aug 14 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Miller, T. W., Cherney, M. M., Lee, A. J., Francolean, N. E., Farmer, P. J., King, S. B., Hobbs, A. J., Miranda, K. M., Burstyn, J. N., & Fukuto, J. M. (2009). The effects of nitroxyl (HNO) on soluble guanylate cyclase activity. Interactions at ferrous heme and cysteine thiols. Journal of Biological Chemistry, 284(33), 21788-21796. https://doi.org/10.1074/jbc.M109.014282