3qwi

Crystal structure of a 17beta-hydroxysteroid dehydrogenase (holo form) from fungus Cochliobolus lunatus in complex with NADPH and coumestrol

spinqualitylabelsall models 3qwi, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qwi 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: CUE, EDO, NAP Related: 3is3, 3itd, 3qwf, 3qwh 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 The 17beta-HSD (17beta-hydroxysteroid dehydrogenase) from the filamentous fungus Cochliobolus lunatus (17beta-HSDcl) is a NADP(H)-dependent enzyme that preferentially catalyses the interconversion of inactive 17-oxo-steroids and their active 17beta-hydroxy counterparts. 17beta-HSDcl belongs to the SDR (short-chain dehydrogenase/reductase) superfamily. It is currently the only fungal 17beta-HSD member that has been described and represents one of the model enzymes of the cP1 classical subfamily of NADPH-dependent SDR enzymes. A thorough crystallographic analysis has been performed to better understand the structural aspects of this subfamily and provide insights into the evolution of the HSD enzymes. The crystal structures of the 17beta-HSDcl apo, holo and coumestrol-inhibited ternary complex, and the active-site Y167F mutant reveal subtle conformational differences in the substrate-binding loop that probably modulate the catalytic activity of 17beta-HSDcl. Coumestrol, a plant-derived non-steroidal compound with oestrogenic activity, inhibits 17beta-HSDcl [IC50 2.8 muM; at 100 muM substrate (4-oestrene-3,17-dione)] by occupying the putative steroid-binding site. In addition to an extensive hydrogen-bonding network, coumestrol binding is stabilized further by pi-pi stacking interactions with Tyr212. A stopped-flow kinetic experiment clearly showed the coenzyme dissociation as the slowest step of the reaction and, in addition to the low steroid solubility, it prevents the accumulation of enzyme-coenzyme-steroid ternary complexes. Insights into subtle conformational differences in the substrate-binding loop of fungal 17beta-hydroxysteroid dehydrogenase: a combined structural and kinetic approach.,Cassetta A, Krastanova I, Kristan K, Brunskole Svegelj M, Lamba D, Lanisnik Rizner T, Stojan J Biochem J. 2012 Jan 1;441(1):151-60. PMID:21929506 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hydroxysteroid dehydrogenase 3D structures

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