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4l1x
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal Structuer of Human 3-alpha Hydroxysteroid Dehydrogenase Type 3 V54L Mutant in Complex with NADP+ and Progesterone== | |
| - | + | <StructureSection load='4l1x' size='340' side='right' caption='[[4l1x]], [[Resolution|resolution]] 2.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[4l1x]] is a 2 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=4L1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L1X FirstGlance]. <br> | |
| - | ==Disease== | + | </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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l1w|4l1w]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKR1C2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4l1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l1x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l1x RCSB], [http://www.ebi.ac.uk/pdbsum/4l1x 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> | [[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 == | |
| - | ==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> | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3) has an essential role in the inactivation of 5alpha-dihydrotestosterone (DHT). Notably, human 3alpha-HSD3 shares 97.8% sequence identity with human 20-alpha hydroxysteroid dehydrogenase (20alpha-HSD) and there is only one amino acid difference (residue 54) that is located in their steroid binding pockets. However, 20alpha-HSD displays a distinctive ability in transforming progesterone to 20alpha-hydroxy-progesterone (20alpha-OHProg). In this study, to understand the role of residue 54 in the steroid binding and discrimination, the V54L mutation in human 3alpha-HSD3 has been created. We have solved two crystal structures of the 3alpha-HSD3.NADP(+).Progesterone complex and the 3alpha-HSD3 V54L.NADP(+).progesterone complex. Interestingly, progesterone adopts two different binding modes to form complexes within the wild type enzyme, with one binding mode similar to the orientation of a bile acid (ursodeoxycholate) in the reported ternary complex of human 3alpha-HSD3.NADP(+).ursodeoxycholate and the other binding mode resembling the orientation of 20alpha-OHProg in the ternary complex of human 20alpha-HSD.NADP(+).20alpha-OHProg. However, the V54L mutation directly restricts the steroid binding modes to a unique one, which resembles the orientation of 20alpha-OHProg within human 20alpha-HSD. Furthermore, the kinetic study has been carried out. The results show that the V54L mutation significantly decreases the 3alpha-HSD activity for the reduction of DHT, while this mutation enhances the 20alpha-HSD activity to convert progesterone. | ||
| - | + | Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3): The V54L mutation restricting the steroid alternative binding and enhancing the 20alpha-HSD activity.,Zhang B, Zhu DW, Hu XJ, Zhou M, Shang P, Lin SX J Steroid Biochem Mol Biol. 2014 May;141:135-43. doi:, 10.1016/j.jsbmb.2014.01.003. Epub 2014 Jan 13. PMID:24434280<ref>PMID:24434280</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Hu, X J | + | == References == |
| - | [[Category: Lin, S X | + | <references/> |
| - | [[Category: Zhang, B | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Hu, X J]] | ||
| + | [[Category: Lin, S X]] | ||
| + | [[Category: Zhang, B]] | ||
[[Category: Akr]] | [[Category: Akr]] | ||
[[Category: Akr1c2]] | [[Category: Akr1c2]] | ||
Revision as of 08:46, 5 January 2015
Crystal Structuer of Human 3-alpha Hydroxysteroid Dehydrogenase Type 3 V54L Mutant in Complex with NADP+ and Progesterone
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Categories: Human | Hu, X J | Lin, S X | Zhang, B | Akr | Akr1c2 | Aldo-keto reductase | Alpha-beta barrel | Human 3-alpha hsd3 | Nadph | Oxidoreductase
