2bf4

From Proteopedia

(Difference between revisions)

Current revision

A second FMN-binding site in yeast NADPH-cytochrome P450 reductase suggests a novel mechanism of electron transfer by diflavin reductases.

Structural highlights

2bf4 is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2bf4"

@@ Line 1: / Line 1: @@
-[[Image:2bf4.gif|left|200px]]<br />
-<applet load="2bf4" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2bf4, resolution 3.00&Aring;" />
-'''A SECOND FMN-BINDING SITE IN YEAST NADPH-CYTOCHROME P450 REDUCTASE SUGGESTS A NOVEL MECHANISM OF ELECTRON TRANSFER BY DIFLAVIN REDUCTASES.'''<br />
-==Overview==
+==A second FMN-binding site in yeast NADPH-cytochrome P450 reductase suggests a novel mechanism of electron transfer by diflavin reductases.==
-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).
+<StructureSection load='2bf4' size='340' side='right'caption='[[2bf4]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2bf4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BF4 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bf4 OCA], [https://pdbe.org/2bf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bf4 RCSB], [https://www.ebi.ac.uk/pdbsum/2bf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bf4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NCPR_YEAST 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.<ref>PMID:1730736</ref> <ref>PMID:9368374</ref> <ref>PMID:9468503</ref> <ref>PMID:11485306</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bf/2bf4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bf4 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== 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).
-==About this Structure==
+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<ref>PMID:16407065</ref>
-BF4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with SO4, FAD, FMN and NAP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NADPH--hemoprotein_reductase NADPH--hemoprotein reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.2.4 1.6.2.4] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BF4 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16407065 16407065]
+</div>
-[[Category: NADPH--hemoprotein reductase]]
+<div class="pdbe-citations 2bf4" style="background-color:#fffaf0;"></div>
-[[Category: Saccharomyces cerevisiae]]
-[[Category: Single protein]]
-[[Category: Kelly, S.L.]]
-[[Category: Kim, Y.]]
-[[Category: Lamb, D.C.]]
-[[Category: Lepesheva, G.I.]]
-[[Category: Podust, L.M.]]
-[[Category: Waterman, M.R.]]
-[[Category: Yermalitskaya, L.V.]]
-[[Category: Yermalitsky, V.N.]]
-[[Category: FAD]]
-[[Category: FMN]]
-[[Category: NAP]]
-[[Category: SO4]]
-[[Category: cpr]]
-[[Category: diflavin reductase]]
-[[Category: electron transfer]]
-[[Category: fad]]
-[[Category: fmn]]
-[[Category: nadp]]
-[[Category: nadph-cytochrome p450 reductase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 17:36:13 2007''
+==See Also==
+*[[NADPH-Cytochrome P450 Reductase|NADPH-Cytochrome P450 Reductase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae]]
+[[Category: Kelly SL]]
+[[Category: Kim Y]]
+[[Category: Lamb DC]]
+[[Category: Lepesheva GI]]
+[[Category: Podust LM]]
+[[Category: Waterman MR]]
+[[Category: Yermalitskaya LV]]
+[[Category: Yermalitsky VN]]

2bf4

From Proteopedia

Current revision

A second FMN-binding site in yeast NADPH-cytochrome P450 reductase suggests a novel mechanism of electron transfer by diflavin reductases.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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