1ihi
From Proteopedia
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| - | + | ==Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate== | |
| - | + | <StructureSection load='1ihi' size='340' side='right' caption='[[1ihi]], [[Resolution|resolution]] 3.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[1ihi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IHI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IHI FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IU5:ISO-URSODEOXYCHOLIC+ACID'>IU5</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-alpha-hydroxycholanate_dehydrogenase 3-alpha-hydroxycholanate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.52 1.1.1.52] </span></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ihi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ihi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ihi RCSB], [http://www.ebi.ac.uk/pdbsum/1ihi PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/AK1C2_HUMAN AK1C2_HUMAN]] Defects in AKR1C2 are a cause of 46,XY sex reversal type 8 (SRXY8) [MIM:[http://omim.org/entry/614279 614279]]. A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.<ref>PMID:21802064</ref> | ||
| + | == Function == | ||
| + | [[http://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> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ih/1ihi_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase (HSD)/bile acid binding protein (AKR1C2) complexed with NADP(+) and 3alpha,7beta-dihydroxy-5beta-cholanic acid (ursodeoxycholate) at 3.0 A resolution is presented. Thus, the three-dimensional structure has now been solved for a human HSD member of the aldo-keto reductase superfamily. AKR1C2 is implicated in the prostatic production of the potent androgen 5alpha-dihydrotestosterone and the hepatic transport of bile acids. It also catalyzes the formation of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in the central nervous system, and its allosteric modulation by fluoxetine has been linked to the use of this drug for premenstrual dsyphoria. Like other members of the superfamily, AKR1C2 folds into an alpha/beta-barrel and binds NADP(+) in an extended conformation. The carboxylate of ursodeoxycholate binds to AKR1C2 in the oxyanion hole at the active site. More interestingly, the orientation of ursodeoxycholate is essentially "backwards" and "upside-down" from that observed for testosterone in the related rat 3alpha-HSD.NADP(+).testosterone ternary complex, where testosterone assumes the position of a 3-ketosteroid substrate. The orientation of ursodeoxycholate is thus similar to that expected of a 17beta-HSD substrate. The ternary structure explains the ability of AKR1C2 to catalyze 3alpha-, 17beta-, and 20alpha-HSD reactions. Comparison of the steroid binding pocket of AKR1C2 with that of rat 3alpha-HSD reveals significant differences in the positions of conserved and nonconserved loop residues, providing insights into the structural basis for the functional flexibility that is observed in all the human 3alpha-HSD isoforms but not in the rat isoform. | ||
| - | + | Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP(+) and ursodeoxycholate.,Jin Y, Stayrook SE, Albert RH, Palackal NT, Penning TM, Lewis M Biochemistry. 2001 Aug 28;40(34):10161-8. PMID:11513593<ref>PMID:11513593</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]] | *[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: 3-alpha-hydroxycholanate dehydrogenase]] | [[Category: 3-alpha-hydroxycholanate dehydrogenase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
Revision as of 14:16, 29 September 2014
Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate
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