title: Structure of bacterial 3beta/17beta-hydroxysteroid dehydrogenase at 1.2 A resolution: a model for multiple steroid recognition.
abstract: The enzyme 3beta/17beta-hydroxysteroid dehydrogenase (3beta/17beta-HSD) is a steroid-inducible component of the Gram-negative bacterium Comamonas testosteroni. It catalyzes the reversible reduction/dehydrogenation of the oxo/beta-hydroxy groups at positions 3 and 17 of steroid compounds, including hormones and isobile acids. Crystallographic analysis at 1.2 A resolution reveals the enzyme to have nearly identical subunits that form a tetramer with 222 symmetry. This is one of the largest oligomeric structures refined at this resolution. The subunit consists of a monomer with a single-domain structure built around a seven-stranded beta-sheet flanked by six alpha-helices. The active site contains a Ser-Tyr-Lys triad, typical for short-chain dehydrogenases/reductases (SDR). Despite their highly diverse substrate specificities, SDR members show a close to identical folding pattern architectures and a common catalytic mechanism. In contrast to other SDR apostructures determined, the substrate binding loop is well-defined. Analysis of structure-activity relationships of catalytic cleft residues, docking analysis of substrates and inhibitors, and accessible surface analysis explains how 3beta/17beta-HSD accommodates steroid substrates of different conformations.
authors.affiliation: Karolinska Institutet NOVUM, Center for Structural Biochemistry, S-14157 Huddinge, Sweden.
authors.forename: Jordi
authors.initials: J
authors.lastname: Benach
authors.forename: Charlotta
authors.initials: C
authors.lastname: Filling
authors.forename: Udo C T
authors.initials: UC
authors.lastname: Oppermann
authors.forename: Pietro
authors.initials: P
authors.lastname: Roversi
authors.forename: Gérard
authors.initials: G
authors.lastname: Bricogne
authors.forename: Kurt D
authors.initials: KD
authors.lastname: Berndt
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.forename: Rudolf
authors.initials: R
authors.lastname: Ladenstein
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry* / Q000235:genetics; D000728:Androgens / Q000737:chemistry; D001051:Apoenzymes / Q000737:chemistry / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001647:Bile Acids and Salts / Q000737:chemistry; D001665:Binding Sites / Q000235:genetics; D020604:Comamonas testosteroni / Q000201:enzymology* / Q000235:genetics; D018360:Crystallography, X-Ray; D004967:Estrogens / Q000737:chemistry; D008958:Models, Molecular; D017354:Point Mutation; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000235:genetics; D013237:Stereoisomerism; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D000728:Androgens; D001051:Apoenzymes; D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D004967:Estrogens; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase