rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2003-1-17
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pubmed:abstractText |
Two distinct genes encode the human type 1 (placenta, mammary gland) and type 2 (adrenal, gonad) isoforms of 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD). We have produced the Y154F, H156Y, and K158Q mutant enzymes in the Y154-P-H156-S-K158 motif of the human type 1 3beta-HSD/isomerase. The H156Y mutant was created to produce a chimera of the type 2 enzyme motif (Y154-P-Y156-S-K158) in the type 1 enzyme. The wild-type (WT) 1 and 2 plus the mutant enzymes were expressed and purified. The Km for dehydroepiandrosterone and Ki for epostane measured with both the H156Y mutant and WT 2 are 13-fold to 17-fold greater than those values obtained with the WT 1 3beta-HSD. The Y154F and K158Q mutants exhibit no 3beta-HSD but have significant isomerase activity. Thus, H156 in WT 1 vs. Y156 in WT 2 accounts for the substantially higher affinity of WT 1 3beta-HSD activity for these substrate and inhibitor steroids relative to the WT 2 enzyme.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Nov
|
pubmed:issn |
0743-5800
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
471-5
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12530651-Androstenols,
pubmed-meshheading:12530651-Animals,
pubmed-meshheading:12530651-Cell Line,
pubmed-meshheading:12530651-Dehydroepiandrosterone,
pubmed-meshheading:12530651-Enzyme Inhibitors,
pubmed-meshheading:12530651-Humans,
pubmed-meshheading:12530651-Insects,
pubmed-meshheading:12530651-Isoenzymes,
pubmed-meshheading:12530651-Kinetics,
pubmed-meshheading:12530651-Multienzyme Complexes,
pubmed-meshheading:12530651-Mutation,
pubmed-meshheading:12530651-Progesterone Reductase,
pubmed-meshheading:12530651-Steroid Isomerases
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pubmed:year |
2002
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pubmed:articleTitle |
Differences in substrate and inhibitor kinetics of human type 1 and type 2 3beta-hydroxysteroid dehydrogenase are explained by the type 1 mutant, H156Y.
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pubmed:affiliation |
Mercer University School of Medicine, Macon, GA 31207, USA. thomas_j@mercer.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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