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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.

SUBMITTER: Fritz BG

PROVIDER: S-EPMC3128461 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Fritz Bradley G BG Hu Xiaohui X Brailey Jacqueline L JL Berry Robert E RE Walker F Ann FA Montfort William R WR

Biochemistry 20110610 26

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 h ...[more]

PMID: 21639146

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