ArticleThe Journal of biological chemistry2012
Heme-assisted S-nitrosation desensitizes ferric soluble guanylate cyclase to nitric oxide.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- Soluble guanylyl cyclase maturation in cells depends on reduction of the incoming heme by a cysteine in the enzyme's beta subunit.The Journal of biological chemistry · 2026Article
- A Nutraceutical Approach for Hypertension: Randomized Controlled Trial of Grape Pomace Extract and L-Arginine.Antioxidants (Basel, Switzerland) · 2026Article
- Key roles of GAPDH, Hsp90, and NO in heme trafficking.Journal of inorganic biochemistry · 2026Review
- Flipping Off and On the Redox Switch in the Microcirculation.Annual review of physiology · 2023Review
- Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase.Cells · 2023Review
- NO and Heme Proteins: Cross-Talk between Heme and Cysteine Residues.Antioxidants (Basel, Switzerland) · 2023Review
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals.Biological chemistry · 2022Review
- Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease.International journal of molecular sciences · 2022Review
- Smooth muscle cell CYB5R3 preserves cardiac and vascular function under chronic hypoxic stress.Journal of molecular and cellular cardiology · 2022Article
- Nitric oxide and heme-NO stimulate superoxide production by NADPH oxidase 5.Free radical biology & medicine · 2021Article
- Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds.Molecules (Basel, Switzerland) · 2021Review
- Higher susceptibility to heme oxidation and lower protein stability of the rare αBiochemical pharmacology · 2021Article
- Wavelength- and irradiance-dependent changes in intracellular nitric oxide level.Journal of biomedical optics · 2020Article
- Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease.Scientific reports · 2020Article
- Article
- Biochemical basis and metabolic interplay of redox regulation.Redox biology · 2019Review
- Heat shock protein 90 regulates soluble guanylyl cyclase maturation by a dual mechanism.The Journal of biological chemistry · 2019Article
- Structure/function of the soluble guanylyl cyclase catalytic domain.Nitric oxide : biology and chemistry · 2018Review
- Physiological activation and deactivation of soluble guanylate cyclase.Nitric oxide : biology and chemistry · 2018Review
- The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Nitric oxide (NO) signaling regulates key processes in cardiovascular physiology, specifically vasodilation, platelet aggregation, and leukocyte rolling. Soluble guanylate cyclase (sGC), the mammalian NO sensor, transduces an NO signal into the classical second messenger cyclic GMP (cGMP). NO binds to the ferrous (Fe(2+)) oxidation state of the sGC heme cofactor and stimulates formation of cGMP several hundred-fold. Oxidation of the sGC heme to the ferric (Fe(3+)) state desensitizes the enzyme to NO. The heme-oxidized state of sGC has emerged as a potential therapeutic target in the treatment of cardiovascular disease. Here, we investigate the molecular mechanism of NO desensitization and find that sGC undergoes a reductive nitrosylation reaction that is coupled to the S-nitrosation of sGC cysteines. We further characterize the kinetics of NO desensitization and find that heme-assisted nitrosothiol formation of β1Cys-78 and β1Cys-122 causes the NO desensitization of ferric sGC. Finally, we provide evidence that the mechanism of reductive nitrosylation is gated by a conformational change of the protein. These results yield insights into the function and dysfunction of sGC in cardiovascular disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.