Molecular Mechanism Study on Stereo-Selectivity of α or β Hydroxysteroid Dehydrogenases

Hydroxysteroid dehydrogenases (HSDHs) are from two superfamilies of short-chain dehydrogenase (SDR) and aldo–keto reductase (AKR). The HSDHs were summarized classified according to their structural functional differences. A typical pair enzymes, 7α–hydroxysteroid (7α–HSDH) 7β–hydroxysteroid (7β–HSDH), have been reported before. Molecular docking 7-keto–lithocholic acid(7–KLA) the binary 7β–HSDH nicotinamide adenine dinucleotide phosphate (NADP+) was realized via YASARA, a possible binding model 7–KLA obtained. α side towards NADP+ in 7β–HSDH, while β (NAD+) 7α–HSDH, made orientations C7–OH different products. interaction between Ser193 pyrophosphate NAD(P)+ [Ser193–OG⋯3.11Å⋯O1N–PN] caused upturning PN–phosphate group, which formed barrier with chain His95 make only able bind NADP+. Tyr253 C24 may contribute formation substrate orientation 7β–HSDH. results sequence alignment showed conservation His95, Ser193, 7β–HSDHs, exhibiting significant difference 7α–HSDHs. molecular other 17β–HSDH SDR superfamily 3(17)α–HSDH AKR superfamily, has furtherly verified that stereospecificity related orientation.