ArticleThe Journal of biological chemistry2014
NO* binds human cystathionine β-synthase quickly and tightly.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Harnessing gasotransmitters for orthopaedic infection therapy: Mechanisms and advanced delivery platforms.Bioactive materials · 2027Review
- Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer's and Parkinson's diseases.Redox report : communications in free radical research · 2026Review
- Structure and function of persulfide dioxygenase fromiScience · 2026Article
- The role of gasotransmitters in Parkinson's disease: Interplay of nitric oxide, carbon monoxide, and hydrogen sulfide.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Utility of NO and HNitric oxide : biology and chemistry · 2022Review
- Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response.Pharmacological reviews · 2022Review
- Gases in Sepsis: Novel Mediators and Therapeutic Targets.International journal of molecular sciences · 2022Review
- Early processes in heme-based CO-sensing proteins.Frontiers in molecular biosciences · 2022Review
- Structural Basis for Allostery in PLP-dependent Enzymes.Frontiers in molecular biosciences · 2022Review
- Human Cystathionine γ-Lyase Is Inhibited byAntioxidants (Basel, Switzerland) · 2021Article
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
- Cysteine metabolic circuitries: druggable targets in cancer.British journal of cancer · 2021Review
- Article
- Interaction among Hydrogen Sulfide and Other Gasotransmitters in Mammalian Physiology and Pathophysiology.Advances in experimental medicine and biology · 2021Review
- Hydrogen Sulfide: From a Toxic Molecule to a Key Molecule of Cell Life.Antioxidants (Basel, Switzerland) · 2020Review
- Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase.Redox biology · 2020Article
- Hydrogen Sulfide Metabolism and Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2020Review
- The Role of Host-Generated HFrontiers in cellular and infection microbiology · 2020Review
- Screening Pyridine Derivatives against Human Hydrogen Sulfide-synthesizing Enzymes by Orthogonal Methods.Scientific reports · 2019Article
- Hydrogen Sulfide Oxidation: Adaptive Changes in Mitochondria of SW480 Colorectal Cancer Cells upon Exposure to Hypoxia.Oxidative medicine and cellular longevity · 2019Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hexa-coordinate heme in the H2S-generating human enzyme cystathionine β-synthase (CBS) acts as a redox-sensitive regulator that impairs CBS activity upon binding of NO(•) or CO at the reduced iron. Despite the proposed physiological relevance of this inhibitory mechanism, unlike CO, NO(•) was reported to bind at the CBS heme with very low affinity (Kd = 30-281 μm). This discrepancy was herein reconciled by investigating the NO(•) reactivity of recombinant human CBS by static and stopped-flow UV-visible absorption spectroscopy. We found that NO(•) binds tightly to the ferrous CBS heme, with an apparent Kd ≤ 0.23 μm. In line with this result, at 25 °C, NO(•) binds quickly to CBS (k on ∼ 8 × 10(3) m(-1) s(-1)) and dissociates slowly from the enzyme (k off ∼ 0.003 s(-1)). The observed rate constants for NO(•) binding were found to be linearly dependent on [NO(•)] up to ∼ 800 μm NO(•), and >100-fold higher than those measured for CO, indicating that the reaction is not limited by the slow dissociation of Cys-52 from the heme iron, as reported for CO. For the first time the heme of human CBS is reported to bind NO(•) quickly and tightly, providing a mechanistic basis for the in vivo regulation of the enzyme by NO(•). The novel findings reported here shed new light on CBS regulation by NO(•) and its possible (patho)physiological relevance, enforcing the growing evidence for an interplay among the gasotransmitters NO(•), CO, and H2S in cell signaling.
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