Molecular cloning of human type 3 3 alpha-hydroxysteroid dehydrogenase that differs from 20 alpha-hydroxysteroid dehydrogenase by seven amino acids.
We have isolated, by screening a lambda gt11 human prostatic cDNA library, a cDNA clone that shows after transfection into transformed human embryonal kidney (293) cells high 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity that catalyzes efficiently the transformation of dihydrotestosterone to 5 alpha-androstane-3 alpha, 17 beta-diol. Chronologically, we name this enzyme type 3 3 alpha-HSD (3 alpha-HSD3). Surprisingly, human 3 alpha-HSD3 shares much higher amino acids sequence identity with human 20 alpha-HSD (97.8%) than with human type 1 and type 2 3 alpha-HSD (81.1 and 85.7% identity, respectively). DNA analysis predicts a protein of 323 amino acids with a molecular mass of 36,844. Alignment of the amino acid sequence of 3 alpha-HSD3 with other related 3 alpha- and 20 alpha-HSDs indicates that 3 alpha-HSD3 shares 68.1, 78.3, and 67.4% identity with rat 3 alpha-HSD and rabbit and rat 20 alpha-HSD, respectively. 3 alpha-HSD3 belongs to the aldo-keto reductase family and like almost all the members of this family preferred NADPH as cofactor.
Dufort
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Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
Soucy
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Labrie
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D015089:20-Hydroxysteroid Dehydrogenases / Q000737:chemistry*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D015096:3-Hydroxysteroid Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D015723:Gene Library; D006801:Humans; D007668:Kidney; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011467:Prostate / Q000201:enzymology; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014162:Transfection
D011994:Recombinant Proteins; D015096:3-Hydroxysteroid Dehydrogenases; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)