Structural highlights
Function
[HMOX1_RAT] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
Publication Abstract from PubMed
Heme oxygenase-1 (HMOX1) catalyzes heme degradation utilizing reducing equivalents supplied from NADPH-cytochrome P450 reductase (CYPOR). Recently, we determined the complex structure of NADP(+) -bound open-conformation stabilized CYPOR and heme-HMOX1, but the resolution was limited to 4.3 A. Here, we determined the crystal structure of the fusion protein of open-conformation stabilized CYPOR and heme-HMOX1 at 3.25 A resolution. Unexpectedly, no NADP(+) was bound to this fusion protein in the crystal. Structural comparison of the NADP(+) -bound complex and the NADP(+) -free fusion protein suggests that NADP(+) binding regulates the conformational change in the FAD-binding domain of CYPOR. As a result of this change, the FMN-binding domain of CYPOR approaches heme-bound HMOX1 upon NADP(+) binding to enhance the electron-transfer efficiency from FMN to heme.
Crystal structure of a NADPH-cytochrome P450 oxidoreductase (CYPOR) and heme oxygenase 1 fusion protein implies a conformational change in CYPOR upon NADPH/NADP(+) binding.,Sugishima M, Sato H, Wada K, Yamamoto K FEBS Lett. 2019 Mar 18. doi: 10.1002/1873-3468.13360. PMID:30883732[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sugishima M, Sato H, Wada K, Yamamoto K. Crystal structure of a NADPH-cytochrome P450 oxidoreductase (CYPOR) and heme oxygenase 1 fusion protein implies a conformational change in CYPOR upon NADPH/NADP(+) binding. FEBS Lett. 2019 Mar 18. doi: 10.1002/1873-3468.13360. PMID:30883732 doi:http://dx.doi.org/10.1002/1873-3468.13360
