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 R. Montfort

doi:10.1021/bi200794c

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 R. 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 language	English (US)
Pages (from-to)	5813-5815
Number of pages	3
Journal	Biochemistry
Volume	50
Issue number	26
DOIs	https://doi.org/10.1021/bi200794c
State	Published - Jul 5 2011

ASJC Scopus subject areas

Biochemistry

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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.",

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T1 - Oxidation and loss of heme in soluble guanylyl cyclase from Manduca sexta

AU - Fritz, Bradley G.

AU - Hu, Xiaohui

AU - Brailey, Jacqueline L.

AU - Berry, Robert E.

AU - Walker, F. Ann

AU - Montfort, William R.

PY - 2011/7/5

Y1 - 2011/7/5

N2 - 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.

AB - 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.

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

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