Structural highlights
Function
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.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
NADPH-cytochrome P450 reductase transfers two reducing equivalents derived from a hydride ion of NADPH via FAD and FMN to the large family of microsomal cytochrome P450 monooxygenases in one-electron transfer steps. The mechanism of electron transfer by diflavin reductases remains elusive and controversial. Here, we determined the crystal structure of truncated yeast NADPH-cytochrome P450 reductase, which is functionally active toward its physiological substrate cytochrome P450, and discovered a second FMN binding site at the interface of the connecting and FMN binding domains. The two FMN binding sites have different accessibilities to the bulk solvent and different amino acid environments, suggesting stabilization of different electronic structures of the reduced flavin. Since only one FMN cofactor is required for function, a hypothetical mechanism of electron transfer is discussed that proposes shuttling of a single FMN between these two sites coupled with the transition between two semiquinone forms, neutral (blue) and anionic (red).
A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases.,Lamb DC, Kim Y, Yermalitskaya LV, Yermalitsky VN, Lepesheva GI, Kelly SL, Waterman MR, Podust LM Structure. 2006 Jan;14(1):51-61. PMID:16407065[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Lamb DC, Kim Y, Yermalitskaya LV, Yermalitsky VN, Lepesheva GI, Kelly SL, Waterman MR, Podust LM. A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases. Structure. 2006 Jan;14(1):51-61. PMID:16407065 doi:10.1016/j.str.2005.09.015
