3qwh | pdb_00003qwh

Crystal structure of the 17beta-hydroxysteroid dehydrogenase from Cochliobolus lunatus in complex with NADPH and kaempferol

spinqualitylabelsall models 3qwh, resolution 2.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qwh is a 4 chain structure with sequence from Cbs 730.96. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: KMP, NAP, PEG Related: 3is3, 3itd, 3qwf Gene: 17HSDcl (CBS 730.96) Activity: 17-beta-estradiol 17-dehydrogenase, with EC number 1.1.1.62 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Phytoestrogens are plant-derived compounds that functionally and structurally mimic mammalian estrogens. Phytoestrogens have broad inhibitory activities toward several steroidogenic enzymes, such as the 17beta-hydroxysteroid dehydrogenases (17beta-HSDs), which modulate the biological potency of androgens and estrogens in mammals. However, to date, no crystallographic data are available to explain phytoestrogens binding to mammalian 17beta-HSDs. NADP(H)-dependent 17beta-HSD from the filamentous fungus Cochliobolus lunatus (17beta-HSDcl) has been the subject of extensive biochemical, kinetic and quantitative structure-activity relationship studies that have shown that the flavonols are the most potent inhibitors. In the present study, we investigated the structure-activity relationships of the ternary complexes between the holo form of 17beta-HSDcl and the flavonols kaempferol and 3,7-dihydroxyflavone, in comparison with the isoflavones genistein and biochanin A. Crystallographic data are accompanied by kinetic analysis of the inhibition mechanisms for six flavonols (3-hydroxyflavone, 3,7-dihydroxyflavone, kaempferol, quercetin, fisetin, myricetin), one flavanone (naringenin), one flavone (luteolin), and two isoflavones (genistein, biochanin A). The kinetics analysis shows that the degree of hydroxylation of ring B significantly influences the overall inhibitory efficacy of the flavonols. A distinct binding mode defines the interactions between 17beta-HSDcl and the flavones and isoflavones. Moreover, the complex with biochanin A reveals an unusual binding mode that appears to account for its greater inhibition of 17beta-HSDcl with respect to genistein. Overall, these data provide a blueprint for identification of the distinct molecular determinants that underpin 17beta-HSD inhibition by phytoestrogens. Structural basis for inhibition of 17beta-hydroxysteroid dehydrogenases by phytoestrogens: The case of fungal 17beta-HSDcl.,Cassetta A, Stojan J, Krastanova I, Kristan K, Brunskole Svegelj M, Lamba D, Rizner TL J Steroid Biochem Mol Biol. 2017 Jul;171:80-93. doi: 10.1016/j.jsbmb.2017.02.020., Epub 2017 Mar 1. PMID:28259640 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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