5l7y

17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal inhibitor.17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal inhibitor.

Structural highlights 5l7y is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.912Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DHB14_HUMAN Has NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. Converts oestradiol to oestrone. The physiological substrate is not known. Acts on oestradiol and 5-androstene-3-beta,17-beta-diol (in vitro). Publication Abstract from PubMed 17beta-HSD14 belongs to the SDR family and oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD+ as cofactor. The goal of this study was to identify and optimize 17beta-HSD14 nonsteroidal inhibitors as well as to disclose their structure-activity relationship. In a first screen, a library of 17beta-HSD1 and 17beta-HSD2 inhibitors, selected with respect to scaffold diversity, was tested for 17beta-HSD14 inhibition. The most interesting hit was taken as starting point for chemical modification applying a ligand-based approach. The designed compounds were synthesized and tested for 17beta-HSD14 inhibitory activity. The two best inhibitors identified in this study have a very high affinity to the enzyme with a Ki equal to 7 nM. The strong affinity of these inhibitors to the enzyme active site could be explained by crystallographic structure analysis, which highlighted the role of an extended H-bonding network in the stabilization process. The selectivity of the most potent compounds with respect to 17beta-HSD1 and 17beta-HSD2 is also addressed. First Structure-Activity Relationship of 17beta-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme.,Braun F, Bertoletti N, Moller G, Adamski J, Steinmetzer T, Salah M, Abdelsamie AS, van Koppen CJ, Heine A, Klebe G, Marchais-Oberwinkler S J Med Chem. 2016 Dec 8;59(23):10719-10737. Epub 2016 Nov 18. PMID:27933965 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hydroxysteroid dehydrogenase 3D structures

spinqualitylabelsall models 5l7y, resolution 1.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image