|3fjo, resolution 2.50Å ()|
|Gene:||NCP1, POR (Saccharomyces cerevisiae)|
Structure of chimeric YH CPR
Two catalytic domains, bearing FMN and FAD cofactors, joined by a connecting domain, compose the core of the NADPH cytochrome P450 reductase (CPR). The FMN domain of CPR mediates electron shuttling from the FAD domain to cytochromes P450. Together, both enzymes form the main mixed-function oxidase system that participates in the metabolism of endo- and xenobiotic compounds in mammals. Available CPR structures show a closed conformation, with the two cofactors in tight proximity, which is consistent with FAD-to-FMN, but not FMN-to-P450, electron transfer. Here, we report the 2.5 A resolution crystal structure of a functionally competent yeast-human chimeric CPR in an open conformation, compatible with FMN-to-P450 electron transfer. Comparison with closed structures shows a major conformational change separating the FMN and FAD cofactors from 86 A.
Structure of the open conformation of a functional chimeric NADPH cytochrome P450 reductase., Aigrain L, Pompon D, Morera S, Truan G, EMBO Rep. 2009 Jul;10(7):742-7. Epub 2009 May 29. PMID:19483672
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[NCPR_YEAST] 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. Involved in ergosterol biosynthesis. Has NADPH-dependent ferrireductase activity on the plasma membrane.
About this Structure
- Aigrain L, Pompon D, Morera S, Truan G. Structure of the open conformation of a functional chimeric NADPH cytochrome P450 reductase. EMBO Rep. 2009 Jul;10(7):742-7. Epub 2009 May 29. PMID:19483672 doi:10.1038/embor.2009.82
- ↑ Turi TG, Loper JC. Multiple regulatory elements control expression of the gene encoding the Saccharomyces cerevisiae cytochrome P450, lanosterol 14 alpha-demethylase (ERG11). J Biol Chem. 1992 Jan 25;267(3):2046-56. PMID:1730736
- ↑ Lesuisse E, Casteras-Simon M, Labbe P. Cytochrome P-450 reductase is responsible for the ferrireductase activity associated with isolated plasma membranes of Saccharomyces cerevisiae. FEMS Microbiol Lett. 1997 Nov 1;156(1):147-52. PMID:9368374
- ↑ Venkateswarlu K, Lamb DC, Kelly DE, Manning NJ, Kelly SL. The N-terminal membrane domain of yeast NADPH-cytochrome P450 (CYP) oxidoreductase is not required for catalytic activity in sterol biosynthesis or in reconstitution of CYP activity. J Biol Chem. 1998 Feb 20;273(8):4492-6. PMID:9468503
- ↑ Lamb DC, Warrilow AG, Venkateswarlu K, Kelly DE, Kelly SL. Activities and kinetic mechanisms of native and soluble NADPH-cytochrome P450 reductase. Biochem Biophys Res Commun. 2001 Aug 10;286(1):48-54. PMID:11485306 doi:10.1006/bbrc.2001.5338