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| | ==Crystal structure of the 17beta-hydroxysteroid dehydrogenase from Cochliobolus lunatus== | | ==Crystal structure of the 17beta-hydroxysteroid dehydrogenase from Cochliobolus lunatus== |
| - | <StructureSection load='3qwf' size='340' side='right' caption='[[3qwf]], [[Resolution|resolution]] 1.88Å' scene=''> | + | <StructureSection load='3qwf' size='340' side='right'caption='[[3qwf]], [[Resolution|resolution]] 1.88Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qwf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Coclu Coclu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QWF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QWF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qwf]] is a 8 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=3QWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QWF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.88Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3is3|3is3]], [[3itd|3itd]], [[3qwh|3qwh]], [[3qwi|3qwi]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5503 COCLU])</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=3qwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qwf OCA], [https://pdbe.org/3qwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qwf RCSB], [https://www.ebi.ac.uk/pdbsum/3qwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qwf ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qwf OCA], [http://pdbe.org/3qwf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qwf RCSB], [http://www.ebi.ac.uk/pdbsum/3qwf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qwf 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.
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| - | 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>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3qwf" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]] | + | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 17-beta-estradiol 17-dehydrogenase]] | + | [[Category: Curvularia lunata]] |
| - | [[Category: Coclu]] | + | [[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: Lanisnik-Rizner, T]] | + | [[Category: Lanisnik-Rizner T]] |
| - | [[Category: Stojan, J]] | + | [[Category: Stojan J]] |
| - | [[Category: Cochliobolus lunatus]]
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| - | [[Category: Cytosol]]
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| - | [[Category: Fungi]]
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| - | [[Category: Hydroxysteroid dehydrogenase]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Rossmann fold]]
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| - | [[Category: Sdr steroid]]
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| - | [[Category: Short chain dehydrogenase/reductase]]
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