ArticleBiochemistry2015
The C-terminal heme regulatory motifs of heme oxygenase-2 are redox-regulated heme binding sites.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Beyond the leaderboard: leveraging predictive modeling for protein-ligand insights and discovery.Bioinformatics (Oxford, England) · 2025Article
- 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
- NosP Detection of Heme ModulatesBiochemistry · 2023Article
- Article
- Annotation of biologically relevant ligands in UniProtKB using ChEBI.Bioinformatics (Oxford, England) · 2023Article
- Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase.Biological chemistry · 2022Article
- Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders.Antioxidants (Basel, Switzerland) · 2022Review
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- An Extended C-Terminus, the Possible Culprit for Differential Regulation of 5-Aminolevulinate Synthase Isoforms.Frontiers in molecular biosciences · 2022Review
- Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site.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
- Gasotransmitters in pregnancy: from conception to uterine involution.Biology of reproduction · 2019Review
- 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
- The affinity of MhuD for heme is consistent with a heme degrading function in vivo.Metallomics : integrated biometal science · 2018Article
- Article
- The heme-regulatory motif of nuclear receptor Rev-erbβ is a key mediator of heme and redox signaling in circadian rhythm maintenance and metabolism.The Journal of biological chemistry · 2017Article
- Tight binding of heme to Staphylococcus aureus IsdG and IsdI precludes design of a competitive inhibitor.Metallomics : integrated biometal science · 2017Article
- Heme Oxygenases in Cardiovascular Health and Disease.Physiological reviews · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Heme oxygenase-2 (HO2), an enzyme that catalyzes the conversion of heme to biliverdin, contains three heme regulatory motifs (HRMs) centered at Cys127, Cys265, and Cys282. Previous studies using the soluble form of human HO2 spanning residues 1-288 (HO2sol) have shown that a disulfide bond forms between Cys265 and Cys282 and that, in this oxidized state, heme binds to the catalytic site of HO2sol via His45. However, various mutational and spectroscopic studies have confirmed the involvement of cysteine in Fe(3+)-heme binding upon reduction of the disulfide bond. In an effort to understand how the HRMs are involved in binding of heme to disulfide-reduced HO2sol, in the work described here, we further investigated the properties of Fe(3+)-heme bound to HO2. Specifically, we investigated binding of Fe(3+)-heme to a truncated form of soluble HO2 (residues 213-288; HO2tail) that spans the C-terminal HRMs of HO2 but lacks the catalytic core. We found that HO2tail in the disulfide-reduced state binds Fe(3+)-heme and accounts for the spectral features observed upon binding of heme to the disulfide-reduced form of HO2sol that cannot be attributed to heme binding at the catalytic site. Further analysis revealed that while HO2sol binds one Fe(3+)-heme per monomer of protein under oxidizing conditions, disulfide-reduced HO2sol binds slightly more than two. Both Cys265 and Cys282 were identified as Fe(3+)-heme ligands, and His256 also acts as a ligand to the Cys265-ligated heme. Additionally, Fe(3+)-heme binds with a much weaker affinity to Cys282 than to Cys265, which has an affinity much weaker than that of the His45 binding site in the catalytic core. In summary, disulfide-reduced HO2 has multiple binding sites with varying affinities for Fe(3+)-heme.
Indexed as
Identifiers
What OpenQuestion holds
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.