|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3qwi' size='340' side='right'caption='[[3qwi]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='3qwi' size='340' side='right'caption='[[3qwi]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qwi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cbs_730.96 Cbs 730.96]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QWI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qwi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Curvularia_lunata Curvularia lunata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QWI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CUE:COUMESTROL'>CUE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3is3|3is3]], [[3itd|3itd]], [[3qwf|3qwf]], [[3qwh|3qwh]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CUE:COUMESTROL'>CUE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">17HSDcl ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5503 CBS 730.96])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span></td></tr> | + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qwi OCA], [https://pdbe.org/3qwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qwi RCSB], [https://www.ebi.ac.uk/pdbsum/3qwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qwi ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qwi OCA], [https://pdbe.org/3qwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qwi RCSB], [https://www.ebi.ac.uk/pdbsum/3qwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qwi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/O93874_COCLU O93874_COCLU] |
| - | 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<ref>PMID:21929506</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3qwi" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] | | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 17-beta-estradiol 17-dehydrogenase]] | + | [[Category: Curvularia lunata]] |
| - | [[Category: Cbs 730 96]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brunskole, M]] | + | [[Category: Brunskole M]] |
| - | [[Category: Cassetta, A]] | + | [[Category: Cassetta A]] |
| - | [[Category: Krastanova, I]] | + | [[Category: Krastanova I]] |
| - | [[Category: Kristan, K]] | + | [[Category: Kristan K]] |
| - | [[Category: Lamba, D]] | + | [[Category: Lamba D]] |
| - | [[Category: Rizner, T Lanisnik]] | + | [[Category: Lanisnik Rizner T]] |
| - | [[Category: Stojan, J]] | + | [[Category: Stojan J]] |
| - | [[Category: 17beta-hydroxysteroid dehydrogenase]]
| + | |
| - | [[Category: Cytosol]]
| + | |
| - | [[Category: Flavonoid]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: Phytoestrogen]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Short chain dehydrogenase/reductase]]
| + | |
