Publikationsdatum:
2017-04-26
Beschreibung:
In mammals, bile acids/salts and their glycine and taurine conjugates are effectively recycled through enterohepatic circulation. 7β-Hydroxysteroid dehydrogenases (7β-HSDHs; EC 1.1.1.201), including that from the intestinal microbeCollinsella aerofaciens, catalyse the NADPH-dependent reversible oxidation of secondary bile-acid products to avoid potential toxicity. Here, the first structure of NADP+bound to dimeric 7β-HSDH is presented. In one active site, NADP+adopts a conventional binding mode similar to that displayed in related enzyme structures. However, in the other active site a unique binding mode is observed in which the orientation of the nicotinamide is different. Since 7β-HSDH has become an attractive target owing to the wide and important pharmaceutical use of its product ursodeoxycholic acid, this work provides a more detailed template to support rational protein engineering to improve the enzymatic activities of this useful biocatalyst, further improving the yield of ursodeoxycholic acid and its other applications.
Digitale ISSN:
2053-230X
Thema:
Biologie
,
Chemie und Pharmazie
,
Geologie und Paläontologie
,
Physik
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