ArticleThe Journal of biological chemistry2014
Protein/protein interactions in the mammalian heme degradation pathway: heme oxygenase-2, cytochrome P450 reductase, and biliverdin reductase.
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 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Deciphering cytochrome P450 reductase role in MASLD: molecular mechanisms and pathophysiological implications.Nature reviews. Gastroenterology & hepatology · 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 implication of aberrant NRF2 activation in management of female cancers.Frontiers in oncology · 2025Review
- Allosteric modulation of cytochrome P450 enzymes by the NADPH cytochrome P450 reductase FMN-containing domain.The Journal of biological chemistry · 2023Article
- Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase.Biological chemistry · 2022Article
- Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease.Frontiers in medicine · 2021Review
- Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site.The Journal of biological chemistry · 2020Article
- Conformational Equilibrium of NADPH-Cytochrome P450 Oxidoreductase Is Essential for Heme Oxygenase Reaction.Antioxidants (Basel, Switzerland) · 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
- The Chemical Basis of Intracerebral Hemorrhage and Cell Toxicity With Contributions From Eryptosis and Ferroptosis.Frontiers in cellular neuroscience · 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
- Isolation of blue-green eggshell pigmentation-related genes from Putian duck through RNA-seq.BMC genomics · 2019Article
- EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy.Journal of Cancer · 2019Article
- Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs.Antioxidants & redox signaling · 2018Review
- Endothelial cell α-globin and its molecular chaperone α-hemoglobin-stabilizing protein regulate arteriolar contractility.The Journal of clinical investigation · 2018Article
- A cross-domain charge interaction governs the activity of NO synthase.The Journal of biological chemistry · 2018Article
- Application of methyl-TROSY to a large paramagnetic membrane protein without perdeuteration:Journal of biomolecular NMR · 2018Article
- Restricting the conformational freedom of the neuronal nitric-oxide synthase flavoprotein domain reveals impact on electron transfer and catalysis.The Journal of biological chemistry · 2017Article
- Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs.International journal of inflammation · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Heme oxygenase (HO) catalyzes the rate-limiting step in the O2-dependent degradation of heme to biliverdin, CO, and iron with electrons delivered from NADPH via cytochrome P450 reductase (CPR). Biliverdin reductase (BVR) then catalyzes conversion of biliverdin to bilirubin. We describe mutagenesis combined with kinetic, spectroscopic (fluorescence and NMR), surface plasmon resonance, cross-linking, gel filtration, and analytical ultracentrifugation studies aimed at evaluating interactions of HO-2 with CPR and BVR. Based on these results, we propose a model in which HO-2 and CPR form a dynamic ensemble of complex(es) that precede formation of the productive electron transfer complex. The (1)H-(15)N TROSY NMR spectrum of HO-2 reveals specific residues, including Leu-201, near the heme face of HO-2 that are affected by the addition of CPR, implicating these residues at the HO/CPR interface. Alanine substitutions at HO-2 residues Leu-201 and Lys-169 cause a respective 3- and 22-fold increase in K(m) values for CPR, consistent with a role for these residues in CPR binding. Sedimentation velocity experiments confirm the transient nature of the HO-2 · CPR complex (K(d) = 15.1 μM). Our results also indicate that HO-2 and BVR form a very weak complex that is only captured by cross-linking. For example, under conditions where CPR affects the (1)H-(15)N TROSY NMR spectrum of HO-2, BVR has no effect. Fluorescence quenching experiments also suggest that BVR binds HO-2 weakly, if at all, and that the previously reported high affinity of BVR for HO is artifactual, resulting from the effects of free heme (dissociated from HO) on BVR fluorescence.
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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.