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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1992-8-26
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pubmed:abstractText |
The R-(-) isomer of methyl 1-(2,2-dimethylindan-1-yl)imidazole-5-carboxylate (CGA 214372; 2) strongly inhibited P450-dependent obtusifoliol 14 alpha-demethylase (P450OBT.14DM) (I50 = 8 x 10(-9) M, I50/Km = 5 x 10(-5) in a maize (Zea mays) microsomal preparation. Kinetic studies indicated uncompetitive inhibition with respect to obtusifoliol. The corresponding S-(+) isomer was a 20-fold weaker inhibitor for P450OBT.14DM. The molecular features of a variety of analogues of 2 were related to their potency as inhibitors of P450OBT.14DM in vitro, allowing delineation of the key structural requirements governing inhibition of the demethylase. CGA 214372 proved to have a high degree of selectivity for P450OBT.14DM. This allowed easy distinction of this activity from other P450-dependent activities present in the maize microsomal preparation and gave strong evidence that P450OBT.14DM is a herbicidal target. Microsomal maize P450OBT.14DM and yeast P450LAN.14DM, the only known examples of P450-dependent enzymes carrying out an identical metabolic function in different eukaryotes, showed distinct inhibition patterns with CGA 214372 and ketoconazole, a substituted imidazole anti-mycotic.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azoles,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol 14-Demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/Sterols
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0003-9861
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
297
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
123-31
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:1637175-Azoles,
pubmed-meshheading:1637175-Cytochrome P-450 Enzyme System,
pubmed-meshheading:1637175-Kinetics,
pubmed-meshheading:1637175-Microsomes,
pubmed-meshheading:1637175-Oxidoreductases,
pubmed-meshheading:1637175-Sterol 14-Demethylase,
pubmed-meshheading:1637175-Sterols,
pubmed-meshheading:1637175-Structure-Activity Relationship,
pubmed-meshheading:1637175-Zea mays
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pubmed:year |
1992
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pubmed:articleTitle |
Plant sterol biosynthesis: novel potent and selective inhibitors of cytochrome P450-dependent obtusifoliol 14 alpha-methyl demethylase.
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pubmed:affiliation |
Département d'Enzymologie Cellulaire et Moléculaire, CNRS-UPR 406, Strasbourg, France.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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