ArticleBiochemistry2014
YC-1 binding to the β subunit of soluble guanylyl cyclase overcomes allosteric inhibition by the α subunit.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Characterization of a new model of chemotherapy-induced heart failure with reduced ejection fraction and nephrotic syndrome in Ren-2 transgenic rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Per-ARNT-Sim Domains in Nitric Oxide Signaling by Soluble Guanylyl Cyclase.Journal of molecular biology · 2024Review
- Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response.Pharmacological reviews · 2022Review
- Carbon monoxide signaling and soluble guanylyl cyclase: Facts, myths, and intriguing possibilities.Biochemical pharmacology · 2022Review
- The sGC-cGMP Signaling Pathway as a Potential Therapeutic Target in Doxorubicin-Induced Heart Failure: A Narrative Review.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2022Review
- Activation mechanism of human soluble guanylate cyclase by stimulators and activators.Nature communications · 2021Article
- A new paradigm for gaseous ligand selectivity of hemoproteins highlighted by soluble guanylate cyclase.Journal of inorganic biochemistry · 2021Review
- Instability in a coiled-coil signaling helix is conserved for signal transduction in soluble guanylyl cyclase.Protein science : a publication of the Protein Society · 2019Article
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Physiological activation and deactivation of soluble guanylate cyclase.Nitric oxide : biology and chemistry · 2018Review
- Structure/function of the soluble guanylyl cyclase catalytic domain.Nitric oxide : biology and chemistry · 2018Review
- Redox regulation of soluble guanylyl cyclase.Nitric oxide : biology and chemistry · 2018Review
- Discovery of stimulator binding to a conserved pocket in the heme domain of soluble guanylyl cyclase.The Journal of biological chemistry · 2018Article
- Maprotiline Prevents Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats.Frontiers in pharmacology · 2018Article
- Article
- Affinin (Spilanthol), Isolated from Heliopsis longipes, Induces Vasodilation via Activation of Gasotransmitters and Prostacyclin Signaling Pathways.International journal of molecular sciences · 2017Article
- Thiol-Based Redox Modulation of Soluble Guanylyl Cyclase, the Nitric Oxide Receptor.Antioxidants & redox signaling · 2017Review
- Structure and Activation of Soluble Guanylyl Cyclase, the Nitric Oxide Sensor.Antioxidants & redox signaling · 2017Review
- Inhibition of soluble guanylyl cyclase by small molecules targeting the catalytic domain.FEBS letters · 2016Article
- Heat Shock Protein 90 Associates with the Per-Arnt-Sim Domain of Heme-free Soluble Guanylate Cyclase: IMplications for Enzyme Maturation.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Soluble guanylate cyclase (sGC) is a heterodimeric heme protein and the primary nitric oxide receptor. NO binding stimulates cyclase activity, leading to regulation of cardiovascular physiology and making sGC an attractive target for drug discovery. YC-1 and related compounds stimulate sGC both independently and synergistically with NO and CO binding; however, where the compounds bind and how they work remain unknown. Using linked equilibrium binding measurements, surface plasmon resonance, and domain truncations in Manduca sexta and bovine sGC, we demonstrate that YC-1 binds near or directly to the heme-containing domain of the β subunit. In the absence of CO, YC-1 binds with a Kd of 9-21 μM, depending on the construct. In the presence of CO, these values decrease to 0.6-1.1 μM. Pfizer compound 25 bound ∼10-fold weaker than YC-1 in the absence of CO, whereas compound BAY 41-2272 bound particularly tightly in the presence of CO (Kd = 30-90 nM). Additionally, we found that CO binds much more weakly to heterodimeric sGC proteins (Kd = 50-100 μM) than to the isolated heme domain (Kd = 0.2 μM for Manduca β H-NOX/PAS). YC-1 greatly enhanced binding of CO to heterodimeric sGC, as expected (Kd ∼ 1 μM). These data indicate the α subunit induces a heme pocket conformation with a lower affinity for CO and NO. YC-1 family compounds bind near the heme domain, overcoming the α subunit effect and inducing a heme pocket conformation with high affinity. We propose this high-affinity conformation is required for the full-length protein to achieve high catalytic activity.
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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.