Structural highlights
Function
[NCPR_RAT] This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. [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
NADPH-cytochrome P450 oxidoreductase (CPR) supplies electrons to various heme proteins including heme oxygenase (HO), which is a key enzyme for heme degradation. Electrons from NADPH flow first to flavin adenine dinucleotide, then to flavin mononucleotide (FMN), and finally to heme in the redox partner. For electron transfer from CPR to its redox partner, the closed-open transition of CPR is indispensable. Here, we demonstrate that a hinge-shortened CPR variant, which favors an open conformation, makes a stable complex with heme-HO-1 and can support the HO reaction, although its efficiency is extremely limited. Furthermore, we determined the crystal structure of the CPR variant in complex with heme-HO-1 at 4.3-A resolution. The crystal structure of a complex of CPR and its redox partner was previously unidentified. The distance between heme and FMN in this complex (6 A) implies direct electron transfer from FMN to heme.
Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase.,Sugishima M, Sato H, Higashimoto Y, Harada J, Wada K, Fukuyama K, Noguchi M Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2524-9. doi:, 10.1073/pnas.1322034111. Epub 2014 Feb 3. PMID:24550278[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sugishima M, Sato H, Higashimoto Y, Harada J, Wada K, Fukuyama K, Noguchi M. Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase. Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2524-9. doi:, 10.1073/pnas.1322034111. Epub 2014 Feb 3. PMID:24550278 doi:http://dx.doi.org/10.1073/pnas.1322034111
