4xve: Difference between revisions
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==17beta-HSD5 in complex with 3-pentyl-2-[(pyridin-2-ylmethyl)sulfanyl]-7-(pyrrolidin-1-ylcarbonyl)quinazolin-4(3H)-one== | ==17beta-HSD5 in complex with 3-pentyl-2-[(pyridin-2-ylmethyl)sulfanyl]-7-(pyrrolidin-1-ylcarbonyl)quinazolin-4(3H)-one== | ||
<StructureSection load='4xve' size='340' side='right' caption='[[4xve]], [[Resolution|resolution]] 1.55Å' scene=''> | <StructureSection load='4xve' size='340' side='right'caption='[[4xve]], [[Resolution|resolution]] 1.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4xve]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XVE FirstGlance]. <br> | <table><tr><td colspan='2'>[[4xve]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XVE FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=WDS:3-PENTYL-2-[(PYRIDIN-2-YLMETHYL)SULFANYL]-7-(PYRROLIDIN-1-YLCARBONYL)QUINAZOLIN-4(3H)-ONE'>WDS</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=WDS:3-PENTYL-2-[(PYRIDIN-2-YLMETHYL)SULFANYL]-7-(PYRROLIDIN-1-YLCARBONYL)QUINAZOLIN-4(3H)-ONE'>WDS</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wdt|4wdt]], [[4wdu|4wdu]], [[4wdw|4wdw]], [[4wdx|4wdx]], [[4xvd|4xvd]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wdt|4wdt]], [[4wdu|4wdu]], [[4wdw|4wdw]], [[4wdx|4wdx]], [[4xvd|4xvd]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Testosterone_17-beta-dehydrogenase_(NADP(+)) Testosterone 17-beta-dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.64 1.1.1.64] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Testosterone_17-beta-dehydrogenase_(NADP(+)) Testosterone 17-beta-dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.64 1.1.1.64] </span></td></tr> | ||
<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=4xve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xve OCA], [http://pdbe.org/4xve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xve RCSB], [http://www.ebi.ac.uk/pdbsum/4xve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xve ProSAT]</span></td></tr> | <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=4xve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xve OCA], [http://pdbe.org/4xve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xve RCSB], [http://www.ebi.ac.uk/pdbsum/4xve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xve ProSAT]</span></td></tr> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Amano, Y]] | [[Category: Amano, Y]] | ||
[[Category: Yamaguchi, T]] | [[Category: Yamaguchi, T]] | ||
[[Category: Aldo-keto reductase inhibitor]] | [[Category: Aldo-keto reductase inhibitor]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
Revision as of 02:24, 6 June 2019
17beta-HSD5 in complex with 3-pentyl-2-[(pyridin-2-ylmethyl)sulfanyl]-7-(pyrrolidin-1-ylcarbonyl)quinazolin-4(3H)-one17beta-HSD5 in complex with 3-pentyl-2-[(pyridin-2-ylmethyl)sulfanyl]-7-(pyrrolidin-1-ylcarbonyl)quinazolin-4(3H)-one
Structural highlights
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 PubMedType 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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