Abstract
17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding site and are the starting point for structure-based inhibitor design. The two natural variants (S205 and T205) were characterized and adopt a similar structure.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
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17-Hydroxysteroid Dehydrogenases / metabolism
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Ligands
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Models, Molecular
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Molecular Structure
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Pyridines / chemistry
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Pyridines / pharmacology*
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Steroids / chemistry
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Steroids / pharmacology*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Ligands
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Pyridines
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Steroids
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dihydroxyphenylpyridine methanone
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17-Hydroxysteroid Dehydrogenases
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3 (or 17)-beta-hydroxysteroid dehydrogenase