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

In mammals, bile acids/salts and their glycine and taurine conjugates are effectively recycled through enterohepatic circulation. 7 β -Hydroxysteroid dehydrogenases (7 β -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 β -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 β -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.
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Tags: crystal structure NADP -bound 7 β -HSDH rational protein engineering research communications Source Type: research