2bf4: Difference between revisions

Revision as of 17:37, 21 February 2008

A SECOND FMN-BINDING SITE IN YEAST NADPH-CYTOCHROME P450 REDUCTASE SUGGESTS A NOVEL MECHANISM OF ELECTRON TRANSFER BY DIFLAVIN REDUCTASES.

OverviewOverview

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).

About this StructureAbout this Structure

2BF4 is a Single protein structure of sequence from Saccharomyces cerevisiae with , , and as ligands. Active as NADPH--hemoprotein reductase, with EC number 1.6.2.4 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

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

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OCA

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 ==Overview==
-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).
+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).
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Single protein]]
-[[Category: Kelly, S.L.]]
+[[Category: Kelly, S L.]]
 [[Category: Kim, Y.]]
-[[Category: Lamb, D.C.]]
+[[Category: Lamb, D C.]]
-[[Category: Lepesheva, G.I.]]
+[[Category: Lepesheva, G I.]]
-[[Category: Podust, L.M.]]
+[[Category: Podust, L M.]]
-[[Category: Waterman, M.R.]]
+[[Category: Waterman, M R.]]
-[[Category: Yermalitskaya, L.V.]]
+[[Category: Yermalitskaya, L V.]]
-[[Category: Yermalitsky, V.N.]]
+[[Category: Yermalitsky, V N.]]
 [[Category: FAD]]
 [[Category: FMN]]
@@ Line 34: / Line 34: @@
 [[Category: nadph-cytochrome p450 reductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:23:19 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:37:11 2008''