5GT9

The X-ray structure of 7beta-hydroxysteroid dehydrogenase

Summary for 5GT9

• Entry DOI: 10.2210/pdb5gt9/pdb
• Descriptor: Oxidoreductase, short chain dehydrogenase/reductase family protein, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: short chain dehydrogenase, steroid substrates, oxidoreductase
• Biological source: Collinsella aerofaciens ATCC 25986
• Total number of polymer chains: 2
• Total formula weight: 59054.37

Authors

Wang, F.,Wang, R.,Lv, Z.,Chen, Q.,Huo, X. (deposition date: 2016-08-19, release date: 2017-05-17, Last modification date: 2023-11-08)

Primary citation

Wang, R.,Wu, J.,Jin, D.K.,Chen, Y.,Lv, Z.,Chen, Q.,Miao, Q.,Huo, X.,Wang, F.
Structure of NADP(+)-bound 7 beta-hydroxysteroid dehydrogenase reveals two cofactor-binding modes
Acta Crystallogr F Struct Biol Commun, 73:246-252, 2017

PubMed Abstract: 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 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 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.

PubMed: 28471355
DOI: 10.1107/S2053230X17004460

Experimental method

X-RAY DIFFRACTION (1.7 Å)