1hdc

MECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITORMECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITOR

Structural highlights 1hdc is a 4 chain structure with sequence from "actinomyces_exfoliatus"_waksman_and_curtis_1916 "actinomyces exfoliatus" waksman and curtis 1916. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Activity: 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase, with EC number 1.1.1.53 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed BACKGROUND: Bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD) reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of androstanes and pregnanes and uses nicotinamide adenine dinucleotide as a cofactor. 3 alpha, 20 beta-HSD belongs to a family of short-chain dehydrogenases that has a highly conserved Tyr-X-X-X-Lys sequence. The family includes mammalian enzymes involved in hypertension, digestion, fertility and spermatogenesis. Several members of the enzyme family, including 3 alpha, 20 beta-HSD, are competitively inhibited by glycyrrhizic acid, a steroidal compound found in licorice, and its derivative, carbenoxolone, an anti-inflammatory glucocorticoid. RESULTS: The three-dimensional structure of the enzyme-carbenoxolone complex has been determined and refined at 2.2 A resolution to a crystallographic R-factor of 19.4%. The hemisuccinate side chain of carbenoxolone makes a hydrogen bond with the hydroxyl group of the conserved residue Tyr152 and occupies the position of the nicotinamide ring of the cofactor. The occupancies of the inhibitor in four independent catalytic sites refine to 100%, 95%, 54% and 36%. CONCLUSIONS: The steroid binds at the catalytic site in a mode much like the previously proposed mode of binding of the substrate cortisone. No bound cofactor molecules were found. The varying occupancy of steroid molecules observed in the four catalytic sites is either due to packing differences or indicates a cooperative effect among the four sites. The observed binding accounts for the inhibition of 3 alpha, 20 beta-HSD. Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor.,Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W Structure. 1994 Oct 15;2(10):973-80. PMID:7866748 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hydroxysteroid dehydrogenase

spinqualitylabelsall models 1hdc, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image