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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
1994-10-4
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pubmed:abstractText |
NADPH-cytochrome P450 oxidoreductase transfers electrons from NADPH to cytochrome P450 and catalyzes the one-electron reduction of many drugs and foreign compounds. This enzyme is a flavoprotein containing the cofactors FMN and FAD, which are essential for its function. We have expressed the putative FMN and FAD/NADPH binding domains of P450 reductase and show that these distinct peptides fold correctly to bind their respective cofactors. The FAD/NADPH domain catalyzed the one-electron reduction of a variety of substrates but did not efficiently reduce cytochrome c or cytochrome P450 (as judged by the oxidation of the CYP1A1 substrate 7-ethoxyresorufin). However, the domains could be combined to provide a functional enzyme active in the reduction of cytochrome c and in transferring electrons to cytochrome P450. Both the reconstitution of the domains and the direct binding of cytochrome c to the FMN domain were ionic-strength dependent. The FMN domain containing the hydrophobic membrane anchor sequence was a potent inhibitor of reconstituted monooxygenase activity. These data strongly support the hypothesis that FMN/FAD-containing proteins have evolved as a fusion of two ancestral genes and provide fundamental insights into how this and structurally related proteins, such as nitric oxide synthase and sulfite reductase, have evolved and function.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-113406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-118758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-13058921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-1372827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-1375933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-14007123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-14907713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-1550342,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-1642640,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-1712077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-1929397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-1986412,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-2110108,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-2115516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-2125483,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-2550423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-2708380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-3021733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-3055302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-3085707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-31362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-3145193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-3919392,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-4113125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-4145653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-4155680,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-632295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-6437671,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-6778861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-6784758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-6792195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-6807985,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8078947-821951
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
91
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8710-4
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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pubmed:year |
1994
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pubmed:articleTitle |
Dissection of NADPH-cytochrome P450 oxidoreductase into distinct functional domains.
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pubmed:affiliation |
Imperial Cancer Research Fund, Molecular Pharmacology Unit, University of Dundee, United Kingdom.
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pubmed:publicationType |
Journal Article,
In Vitro
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