Structural and biochemical insights into 7β‐hydroxysteroid dehydrogenase stereoselectivity |
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Authors: | Simone Savino Erica Elisa Ferrandi Federico Forneris Stefano Rovida Sergio Riva Daniela Monti Andrea Mattevi |
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Institution: | 1. Department of Biology and Biotechnology, University of Pavia, Pavia, Italy;2. Istituto di Chimica del Riconoscimento Molecolare, CNR, Milano, Italy |
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Abstract: | Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo‐ and regio‐selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7β‐hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active‐site accessibility, the bases of the specificity for NADP+, and the general architecture of the steroid binding site. Comparison with 7α‐hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C‐terminal extension reshapes the substrate site of the β‐selective enzyme, possibly leading to an inverted orientation of the bound substrate. Proteins 2016; 84:859–865. © 2016 Wiley Periodicals, Inc. |
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Keywords: | biocatalysis short‐chain dehydrogenase steroid stereoselectivity NADP |
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