Structure of NADP+-bound 7?-hydroxysteroid dehydrogenase reveals two cofactor-binding modes.

ABSTRACT: In mammals, bile acids/salts and their glycine and taurine conjugates are effectively recycled through enterohepatic circulation. 7?-Hydroxysteroid dehydrogenases (7?-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 7?-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 7?-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.

SUBMITTER: Wang R 

PROVIDER: S-EPMC5417313 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature