5gt9
The X-ray structure of 7beta-hydroxysteroid dehydrogenase
Structural highlights
FunctionHSDHB_COLAA 7beta-hydroxysteroid dehydrogenase that catalyzes the reduction of the 7-oxo group of 7-oxo-lithocholate (7-oxo-LCA), to yield ursodeoxycholate (UDCA) (PubMed:21181147, PubMed:6954878, PubMed:27006087). As C.aerofaciens is an intestinal bacterium, this enzyme probably contributes to the formation of UDCA in the human colon. UDCA is regarded as a chemopreventive beneficial secondary bile acid due to its low hydrophobicity; it protects hepatocytes and bile duct epithelial cells against necrosis and apoptosis induced by more hydrophobic secondary bile acids like deoxycholate (DCA) (Probable). This enzyme is also able to catalyze the reverse reaction, i.e. the oxidation of the 7beta-hydroxy group of UDCA to 7-oxo-LCA (PubMed:21181147, PubMed:6954878). To a lesser extent, is also active on the taurine- and glycine-conjugates of ursodeoxycholate. It is specific for NADPH/NADP(+) as the electron acceptor/donor since it is not active with NADH/NAD(+) (PubMed:6954878). In the presence of NADPH, 7beta-HSDH can also reduce dehydrocholate (PubMed:21181147). And is also able to oxidize ursocholate (PubMed:27006087).[1] [2] [3] Publication Abstract from PubMedIn mammals, bile acids/salts and their glycine and taurine conjugates are effectively recycled through enterohepatic circulation. 7beta-Hydroxysteroid dehydrogenases (7beta-HSDHs; EC 1.1.1.201), including that from the intestinal microbe Collinsella 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 7beta-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 7beta-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. Structure of NADP+-bound 7beta-hydroxysteroid dehydrogenase reveals two cofactor-binding modes.,Wang R, Wu J, Jin DK, Chen Y, Lv Z, Chen Q, Miao Q, Huo X, Wang F Acta Crystallogr F Struct Biol Commun. 2017 May 1;73(Pt 5):246-252. doi:, 10.1107/S2053230X17004460. Epub 2017 Apr 26. PMID:28471355[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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