Oxidation and loss of heme in soluble guanylyl cyclase from Manduca sexta

Bradley G. Fritz, Xiaohui Hu, Jacqueline L. Brailey, Robert E. Berry, F. Ann Walker, William "Bill" Montfort

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Abstract

Oxidation and loss of heme in soluble guanylyl/guanylate cyclase (sGC), the nitric oxide receptor, is thought to be a major contributor to cardiovascular disease and is the target of compounds BAY 58-2667 and HMR1766. Using spectroelectrochemical titration, we found a truncated sGC to be highly stable in the ferrous state (234 mV) and to bind ferrous heme tightly even in the presence of NO, despite the NO-induced release of the proximal histidine. In contrast, oxidized sGC readily loses ferric heme to myoglobin (0.47 ± 0.02 h-1). Peroxynitrite, the presumed cellular oxidant, readily oxidizes sGC in 5 mM glutathione.

Original languageEnglish (US)
Pages (from-to)5813-5815
Number of pages3
JournalBiochemistry
Volume50
Issue number26
DOIs
Publication statusPublished - Jul 5 2011

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Fritz, B. G., Hu, X., Brailey, J. L., Berry, R. E., Walker, F. A., & Montfort, W. B. (2011). Oxidation and loss of heme in soluble guanylyl cyclase from Manduca sexta. Biochemistry, 50(26), 5813-5815. https://doi.org/10.1021/bi200794c