3dop: Difference between revisions

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{{Seed}}
[[Image:3dop.png|left|200px]]


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==Crystal structure of 5beta-reductase (AKR1D1) in complex with NADP+ and 5beta-dihydrotestosterone, Resolution 2.00A==
The line below this paragraph, containing "STRUCTURE_3dop", creates the "Structure Box" on the page.
<StructureSection load='3dop' size='340' side='right'caption='[[3dop]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<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>
{{STRUCTURE_3dop|  PDB=3dop  |  SCENE=  }}
<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.


===Crystal structure of 5beta-reductase (AKR1D1) in complex with NADP+ and 5beta-dihydrotestosterone, Resolution 2.00A===
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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3dop" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_18848863}}, adds the Publication Abstract to the page
*[[Aldo-keto reductase 3D structures|Aldo-keto reductase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 18848863 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_18848863}}
__TOC__
 
</StructureSection>
==About this Structure==
3DOP is a [[Single protein]] structure of 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=3DOP OCA].
 
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/18848863 18848863]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Pdbx_ordinal=, <PDBx:audit_author.]]
[[Category: Christianson DW]]
[[Category: Bile acid catabolism]]
[[Category: Di Costanzo L]]
[[Category: Cytoplasm]]
[[Category: Drury JE]]
[[Category: Disease mutation]]
[[Category: Penning TM]]
[[Category: Intrahepatic cholestasis]]
[[Category: Lipid metabolism]]
[[Category: Nadp]]
[[Category: Oxidoreductase]]
[[Category: Product]]
[[Category: Steroid metabolism]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 25 21:04:33 2009''

Latest revision as of 15:13, 1 November 2023

Crystal structure of 5beta-reductase (AKR1D1) in complex with NADP+ and 5beta-dihydrotestosterone, Resolution 2.00A

3dop, resolution 2.00Å

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