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4xo6: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4xo6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XO6 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4xo6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XO6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5SD:5ALPHA-ANDROSTAN-3,17-DIONE'>5SD</scene>, <scene name='pdbligand=AOX:(3BETA,5ALPHA)-3-HYDROXYANDROSTAN-17-ONE'>AOX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5SD:5ALPHA-ANDROSTAN-3,17-DIONE'>5SD</scene>, <scene name='pdbligand=AOX:(3BETA,5ALPHA)-3-HYDROXYANDROSTAN-17-ONE'>AOX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4xo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xo6 OCA], [https://pdbe.org/4xo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xo6 RCSB], [https://www.ebi.ac.uk/pdbsum/4xo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xo6 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=4xo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xo6 OCA], [https://pdbe.org/4xo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xo6 RCSB], [https://www.ebi.ac.uk/pdbsum/4xo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xo6 ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/AK1C2_HUMAN AK1C2_HUMAN] Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.<ref>PMID:8573067</ref>  
[https://www.uniprot.org/uniprot/AK1C2_HUMAN AK1C2_HUMAN] Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.<ref>PMID:8573067</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human 3alpha-HSD3 (3alpha-hydroxysteroid dehydrogenase type 3) plays an essential role in the inactivation of the most potent androgen 5alpha-DHT (5alpha-dihydrotestosterone). The present study attempts to obtain the important structure of 3alpha-HSD3 in complex with 5alpha-DHT and to investigate the role of 3alpha-HSD3 in breast cancer cells. We report the crystal structure of human 3alpha-HSD3.NADP(+).A-dione (5alpha-androstane-3,17-dione)/epi-ADT (epiandrosterone) complex, which was obtained by co-crystallization with 5alpha-DHT in the presence of NADP(+) Although 5alpha-DHT was introduced during the crystallization, oxidoreduction of 5alpha-DHT occurred. The locations of A-dione and epi-ADT were identified in the steroid-binding sites of two 3alpha-HSD3 molecules per crystal asymmetric unit. An overlay showed that A-dione and epi-ADT were oriented upside-down and flipped relative to each other, providing structural clues for 5alpha-DHT reverse binding in the enzyme with the generation of different products. Moreover, we report the crystal structure of the 3alpha-HSD3.NADP(+).4-dione (4-androstene-3,17-dione) complex. When a specific siRNA (100 nM) was used to suppress 3alpha-HSD3 expression without interfering with 3alpha-HSD4, which shares a highly homologous active site, the 5alpha-DHT concentration increased, whereas MCF7 cell growth was suppressed. The present study provides structural clues for 5alpha-DHT reverse binding within 3alpha-HSD3, and demonstrates for the first time that down-regulation of 3alpha-HSD3 decreases MCF7 breast cancer cell growth.
Human 3alpha-hydroxysteroid dehydrogenase type 3: structural clues of 5alpha-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth.,Zhang B, Hu XJ, Wang XQ, Theriault JF, Zhu DW, Shang P, Labrie F, Lin SX Biochem J. 2016 Apr 15;473(8):1037-46. doi: 10.1042/BCJ20160083. Epub 2016 Feb, 29. PMID:26929402<ref>PMID:26929402</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4xo6" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

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OCA
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