title: Structural and biochemical insights into 7β-hydroxysteroid dehydrogenase stereoselectivity.
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.
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, Pavia, 27100, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Savino
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR, via Mario Bianco 9, Milano, 20131, Italy.
authors.forename: Erica Elisa
authors.initials: EE
authors.lastname: Ferrandi
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, Pavia, 27100, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Forneris
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, Pavia, 27100, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rovida
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR, via Mario Bianco 9, Milano, 20131, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Riva
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR, via Mario Bianco 9, Milano, 20131, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, Pavia, 27100, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mattevi
mesh_terms: D039903:Actinobacteria / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D009249:NADP / Q000378:metabolism; D011487:Protein Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; C031932:7 beta-hydroxysteroid dehydrogenase
keywords: NADP; biocatalysis; short-chain dehydrogenase; stereoselectivity; steroid