Structure of NADP+-bound 7ß-hydroxysteroid dehydrogenase reveals two cofactor-binding modes.
Acta Crystallogr F Struct Biol Commun
; 73(Pt 5): 246-252, 2017 05 01.
Article
em En
| MEDLINE
| ID: mdl-28471355
ABSTRACT
In mammals, bile acids/salts and their glycine and taurine conjugates are effectively recycled through enterohepatic circulation. 7ß-Hydroxysteroid dehydrogenases (7ß-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 7ß-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 7ß-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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Ácido Ursodesoxicólico
/
Actinobacteria
/
Hidroxiesteroide Desidrogenases
/
NADP
Idioma:
En
Revista:
Acta Crystallogr F Struct Biol Commun
Ano de publicação:
2017
Tipo de documento:
Article