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

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.

• Authors: Bradley G Fritz, Xiaohui Hu, Jacqueline L Brailey, Robert E Berry, F Ann Walker, William R Montfort
• Journal: Biochemistry (Biochemistry) Vol. 50 Issue 26 Pg. 5813-5 (Jul 05 2011) ISSN: 1520-4995 [Electronic] United States
• PMID: 21639146 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Cytoplasmic and Nuclear
• Heme
• Guanylate Cyclase
• Soluble Guanylyl Cyclase

Topics

• Animals
• Guanylate Cyclase (chemistry, metabolism)
• Heme (metabolism)
• Kinetics
• Manduca (enzymology)
• Oxidation-Reduction
• Receptors, Cytoplasmic and Nuclear (chemistry, metabolism)
• Soluble Guanylyl Cyclase