ArticleThe Journal of biological chemistry2012
Role of cysteine residues in heme binding to human heme oxygenase-2 elucidated by two-dimensional NMR spectroscopy.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- MnTnHex-2-PyPAntioxidants (Basel, Switzerland) · 2021Article
- Recent Advances in the Understanding of the Reaction Chemistries of the Heme Catabolizing Enzymes HO and BVR Based on High Resolution Protein Structures.Current medicinal chemistry · 2020Review
- Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy inFuture science OA · 2019Article
- Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs.Antioxidants & redox signaling · 2018Review
- Review
- A mechanism for CO regulation of ion channels.Nature communications · 2018Article
- Regulation of intracellular heme trafficking revealed by subcellular reporters.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Cysteine-independent activation/inhibition of heme oxygenase-2.Medical gas research · 2016Article
- Cysteine Mutational Studies Provide Insight into a Thiol-Based Redox Switch Mechanism of Metal and DNA Binding in FurA from Anabaena sp. PCC 7120.Antioxidants & redox signaling · 2016Article
- Comparison of the Mechanisms of Heme Hydroxylation by Heme Oxygenases-1 and -2: Kinetic and Cryoreduction Studies.Biochemistry · 2016Article
- Spectroscopic studies reveal that the heme regulatory motifs of heme oxygenase-2 are dynamically disordered and exhibit redox-dependent interaction with heme.Biochemistry · 2015Article
- The C-terminal heme regulatory motifs of heme oxygenase-2 are redox-regulated heme binding sites.Biochemistry · 2015Article
- Protein/protein interactions in the mammalian heme degradation pathway: heme oxygenase-2, cytochrome P450 reductase, and biliverdin reductase.The Journal of biological chemistry · 2014Article
- Carbon-carbon bond cleavage in activation of the prodrug nabumetone.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Signaling function of heme oxygenase proteins.Antioxidants & redox signaling · 2014Review
- A review on hemeoxygenase-2: focus on cellular protection and oxygen response.Oxidative medicine and cellular longevity · 2014Review
- Heme sensor proteins.The Journal of biological chemistry · 2013Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human heme oxygenases 1 and 2 (HO-1 and HO-2) degrade heme in the presence of oxygen and NADPH-cytochrome P450 reductase, producing ferrous iron, CO, and biliverdin. HO-1 is an inducible enzyme, but HO-2 is constitutively expressed in selected tissues and is involved in signaling and regulatory processes. HO-2 has three cysteine residues that have been proposed to modulate the affinity for heme, whereas HO-1 has none. Here we use site-specific mutagenesis and two-dimensional NMR of l-[3-(13)C]cysteine-labeled proteins to determine the redox state of the individual cysteines in HO-2 and assess their roles in binding of heme. The results indicate that in the apoprotein, Cys(282) and Cys(265) are in the oxidized state, probably in an intramolecular disulfide bond. The addition of a reducing agent converts them to the reduced, free thiol state. Two-dimensional NMR of site-specific mutants reveals that the redox state of Cys(265) and Cys(282) varies with the presence or absence of other Cys residues, indicating that the microenvironments of the Cys residues are mutually interdependent. Cys(265) appears to be in a relatively hydrophilic, oxidizable environment compared with Cys(127) and Cys(282). Chemical shift data indicate that none of the cysteines stably coordinates to the heme iron atom. In the oxidized state of the apoprotein, heme is bound 2.5-fold more tightly than in the reduced state. This small difference in heme affinity between the oxidized and reduced states of the protein is much less than previously reported, suggesting that it is not a significant factor in the physiological regulation of cellular heme levels.
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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.