ArticleThe Journal of biological chemistry2007
Evidence that the heme regulatory motifs in heme oxygenase-2 serve as a thiol/disulfide redox switch regulating heme binding.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
- Carbon Monoxide: A Context-Dependent Regulator of the Stress Axis.Biomolecules · 2026Review
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Heme Regulatory Motif of Heme Oxygenase-2 Is Involved in the Interaction with NADPH-Cytochrome P450 Reductase and Regulates Enzymatic Activity.International journal of molecular sciences · 2025Article
- The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Anaerobic heme recycling by gut microbes: Important methods for monitoring porphyrin production.Methods in enzymology · 2024Article
- Article
- Pharmacological Significance of Heme Oxygenase 1 in Prostate Cancer.Current issues in molecular biology · 2023Review
- Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase.Biological chemistry · 2022Article
- The evolutionarily conserved arginyltransferase 1 mediates a pVHL-independent oxygen-sensing pathway in mammalian cells.Developmental cell · 2022Article
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance.Cells · 2021Review
- Hypoxic Regulation of the Large-Conductance, Calcium and Voltage-Activated Potassium Channel, BK.Frontiers in physiology · 2021Review
- Immune Modulation by Inhibitors of the HO System.International journal of molecular sciences · 2020Review
- Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel.The Journal of biological chemistry · 2020Article
- The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation.The Journal of biological chemistry · 2020Article
- New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2020Article
- Dynamic and structural differences between heme oxygenase-1 and -2 are due to differences in their C-terminal regions.The Journal of biological chemistry · 2019Article
- Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs.Antioxidants & redox signaling · 2018Review
- Gas Signaling Molecules and Mitochondrial Potassium Channels.International journal of molecular sciences · 2018Review
- A mechanism for CO regulation of ion channels.Nature communications · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Heme oxygenase (HO) catalyzes the O(2)- and NADPH-dependent conversion of heme to biliverdin, CO, and iron. The two forms of HO (HO-1 and HO-2) share similar physical properties but are differentially regulated and exhibit dissimilar physiological roles and tissue distributions. Unlike HO-1, HO-2 contains heme regulatory motifs (HRMs) (McCoubrey, W. K., Jr., Huang, T. J., and Maines, M. D. (1997) J. Biol. Chem. 272, 12568-12574). Here we describe UV-visible, EPR, and differential scanning calorimetry experiments on human HO-2 variants containing single, double, and triple mutations in the HRMs. Oxidized HO-2, which contains an intramolecular disulfide bond linking Cys(265) of HRM1 and Cys(282) of HRM2, binds heme tightly. Reduction of the disulfide bond increases the K(d) for ferric heme from 0.03 to 0.3 microm, which is much higher than the concentration of the free heme pool in cells. Although the HRMs markedly affect the K(d) for heme, they do not alter the k(cat) for heme degradation and do not bind additional hemes. Because HO-2 plays a key role in CO generation and heme homeostasis, reduction of the disulfide bond would be expected to increase intracellular free heme and decrease CO concentrations. Thus, we propose that the HRMs in HO-2 constitute a thiol/disulfide redox switch that regulates the myriad physiological functions of HO-2, including its involvement in the hypoxic response in the carotid body, which involves interactions with a Ca(2+)-activated potassium channel.
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