Heme Regulatory Motif of Heme Oxygenase-2 Is Involved in the Interaction with NADPH–Cytochrome P450 Reductase and Regulates Enzymatic Activity
Mammalian heme oxygenase (HO) catalyzes heme degradation using reducing equivalents supplied by NADPH-cytochrome P450 reductase (CPR). The tertiary structure of the catalytic domain of a constitutively expressed isoform of HO, HO-2, resembles that of the inductive isoform, HO-1, whereas HO-2 has two heme regulatory motifs (HRM) at the proximal portion of the C-terminus, where the disulfide linkage reflects cellular redox conditions and the second heme binding site is located. Here, we report the results of crosslinking experiments, which suggest that HRM is located near the FMN-binding domain of the CPR when it is complexed with HO-2. The enzymatic assay and reduction kinetics results suggest that heme-bound HRM negatively regulates HO-2 activity in vitro. Cellular redox conditions and free heme concentrations may regulate HO-2 activity.
Authors
- Hideaki Sato (ORCID: https://orcid.org/0000-0001-5212-1240)
- Masakazu Sugishima (ORCID: https://orcid.org/0000-0002-0840-4929)
- Junichi Taira (ORCID: https://orcid.org/0000-0002-8438-865X)
- Tomoichirou Kusumoto (ORCID: https://orcid.org/0000-0002-8386-831X)
- Yuichiro Higashimoto (ORCID: https://orcid.org/0000-0003-1382-8598)
- Hiroshi Sakamoto (ORCID: https://orcid.org/0000-0002-8767-2111)
- Ken Yamamoto (ORCID: https://orcid.org/0000-0002-1531-9685)
Institutions
- Kurume University (JP)
- Kyushu Institute of Technology (JP)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-03-05
- DOI
- https://doi.org/10.3390/ijms26052318
- Citations
- 3
- Primary Topic
- Heme Oxygenase-1 and Carbon Monoxide
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Takeda Science Foundation