4xvd

17beta-HSD5 in complex with 4-nitro-2-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}methyl)phenol

spinqualitylabelsall models 4xvd, resolution 2.81Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xvd is a 2 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 2.81Å Ligands: NAP, WDV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AK1C3_HUMAN Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone. Publication Abstract from PubMed Type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD5) is an aldo-keto reductase expressed in the human prostate which catalyzes the conversion of androstenedione to testosterone. Testosterone is converted to 5alpha-dihydrotestosterone, which is present at high concentrations in patients with castration-resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is therefore considered to be a promising therapy for treating CRPC. In the present study, crystal structures of complexes of 17beta-HSD5 with structurally diverse inhibitors derived from high-throughput screening were determined. In the structures of the complexes, various functional groups, including amide, nitro, pyrazole and hydroxyl groups, form hydrogen bonds to the catalytic residues His117 and Tyr55. In addition, major conformational changes of 17beta-HSD5 were observed following the binding of the structurally diverse inhibitors. These results demonstrate interactions between 17beta-HSD5 and inhibitors at the atomic level and enable structure-based drug design for anti-CRPC therapy. Structures of complexes of type 5 17beta-hydroxysteroid dehydrogenase with structurally diverse inhibitors: insights into the conformational changes upon inhibitor binding.,Amano Y, Yamaguchi T, Niimi T, Sakashita H Acta Crystallogr D Biol Crystallogr. 2015 Apr;71(Pt 4):918-27. doi:, 10.1107/S1399004715002175. Epub 2015 Mar 27. PMID:25849402 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Prostaglandin F synthase 3D structures

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