3dop
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 3dop is ON HOLD until Paper Publication Authors: Di Costanzo, L., Drury, J.E., Penning, T.M., Christianson, D.W. Description: Crystal structure of ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of 5beta-reductase (AKR1D1) in complex with NADP+ and 5beta-dihydrotestosterone, Resolution 2.00A== | |
| + | <StructureSection load='3dop' size='340' side='right'caption='[[3dop]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3dop]] 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=3DOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DOP FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BDT:5-BETA-DIHYDROTESTOSTERONE'>BDT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=3dop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dop OCA], [https://pdbe.org/3dop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dop RCSB], [https://www.ebi.ac.uk/pdbsum/3dop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dop ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/AK1D1_HUMAN AK1D1_HUMAN] Defects in AKR1D1 are the cause of congenital bile acid synthesis defect type 2 (CBAS2) [MIM:[https://omim.org/entry/235555 235555]; also known as cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.<ref>PMID:12970144</ref> <ref>PMID:15030995</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AK1D1_HUMAN AK1D1_HUMAN] Efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites. The bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one can also act as substrates. | ||
| + | == 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/do/3dop_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/main_output.php?pdb_ID=3dop ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human steroid 5beta-reductase (aldo-keto reductase (AKR) 1D1) catalyzes reduction of Delta(4)-ene double bonds in steroid hormones and bile acid precursors. We have reported the structures of an AKR1D1-NADP(+) binary complex, and AKR1D1-NADP(+)-cortisone, AKR1D1-NADP(+)-progesterone and AKR1D1-NADP(+)-testosterone ternary complexes at high resolutions. Recently, structures of AKR1D1-NADP(+)-5beta-dihydroprogesterone complexes showed that the product is bound unproductively. Two quite different mechanisms of steroid double bond reduction have since been proposed. However, site-directed mutagenesis supports only one mechanism. In this mechanism, the 4-pro-R hydride is transferred from the re-face of the nicotinamide ring to C5 of the steroid substrate. E120, a unique substitution in the AKR catalytic tetrad, permits a deeper penetration of the steroid substrate into the active site to promote optimal reactant positioning. It participates with Y58 to create a "superacidic" oxyanion hole for polarization of the C3 ketone. A role for K87 in the proton relay proposed using the AKR1D1-NADP(+)-5beta-dihydroprogesterone structure is not supported. | ||
| - | + | Structure and catalytic mechanism of human steroid 5beta-reductase (AKR1D1).,Di Costanzo L, Drury JE, Christianson DW, Penning TM Mol Cell Endocrinol. 2008 Sep 19. PMID:18848863<ref>PMID:18848863</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3dop" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[Aldo-keto reductase 3D structures|Aldo-keto reductase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Christianson DW]] | ||
| + | [[Category: Di Costanzo L]] | ||
| + | [[Category: Drury JE]] | ||
| + | [[Category: Penning TM]] | ||
Current revision
Crystal structure of 5beta-reductase (AKR1D1) in complex with NADP+ and 5beta-dihydrotestosterone, Resolution 2.00A
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