Function, gene organization and protein structures of 11beta-hydroxysteroid dehydrogenase isoforms.
Enzymatic interconversion of active and inactive glucocorticoid hormone is important, and is carried out physiologically by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isoforms, explaining their role in cellular and toxicological processes. Two forms of the enzyme, 11beta-HSD-1 and 11beta-HSD-2, belonging to the protein superfamily of short-chain dehydrogenases/reductases, have been structurally and functionally characterised. Although displaying dehydrogenase and reductase activities in vitro, the dominant in vivo function of the type-1 enzyme might be to work as a reductase, thus generating active cortisol from inactive cortisone precursors. On the other hand, for adrenal glucocorticoids the type-2 enzyme seems to be exclusively a dehydrogenase and, by inactivating glucocorticoids, confers specificity to peripheral mineralocorticoid receptors.
Oppermann
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UC
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. udo.oppermann@mbb.ki.se
Persson
B
B
Jörnvall
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H
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008322:Mammals; D008961:Models, Structural; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D007527:Isoenzymes; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases