3buv

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{{Seed}}
 
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[[Image:3buv.png|left|200px]]
 
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==Crystal structure of human Delta(4)-3-ketosteroid 5-beta-reductase in complex with NADP and HEPES. Resolution: 1.35 A.==
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The line below this paragraph, containing "STRUCTURE_3buv", creates the "Structure Box" on the page.
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<StructureSection load='3buv' size='340' side='right'caption='[[3buv]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3buv]] 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=3BUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BUV FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35&#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=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
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{{STRUCTURE_3buv| PDB=3buv | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3buv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3buv OCA], [https://pdbe.org/3buv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3buv RCSB], [https://www.ebi.ac.uk/pdbsum/3buv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3buv ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bu/3buv_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3buv ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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AKR1D1 (steroid 5beta-reductase) reduces all Delta(4)-3-ketosteroids to form 5beta-dihydrosteroids, a first step in the clearance of steroid hormones and an essential step in the synthesis of all bile acids. The reduction of the carbon-carbon double bond in an alpha,beta-unsaturated ketone by 5beta-reductase is a unique reaction in steroid enzymology because hydride transfer from NADPH to the beta-face of a Delta(4)-3-ketosteroid yields a cis-A/B-ring configuration with an approximately 90 degrees bend in steroid structure. Here, we report the first x-ray crystal structure of a mammalian steroid hormone carbon-carbon double bond reductase, human Delta(4)-3-ketosteroid 5beta-reductase (AKR1D1), and its complexes with intact substrates. We have determined the structures of AKR1D1 complexes with NADP(+) at 1.79- and 1.35-A resolution (HEPES bound in the active site), NADP(+) and cortisone at 1.90-A resolution, NADP(+) and progesterone at 2.03-A resolution, and NADP(+) and testosterone at 1.62-A resolution. Complexes with cortisone and progesterone reveal productive substrate binding orientations based on the proximity of each steroid carbon-carbon double bond to the re-face of the nicotinamide ring of NADP(+). This orientation would permit 4-pro-(R)-hydride transfer from NADPH. Each steroid carbonyl accepts hydrogen bonds from catalytic residues Tyr(58) and Glu(120). The Y58F and E120A mutants are devoid of activity, supporting a role for this dyad in the catalytic mechanism. Intriguingly, testosterone binds nonproductively, thereby rationalizing the substrate inhibition observed with this particular steroid. The locations of disease-linked mutations thought to be responsible for bile acid deficiency are also revealed.
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===Crystal structure of human Delta(4)-3-ketosteroid 5-beta-reductase in complex with NADP and HEPES. Resolution: 1.35 A.===
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Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis.,Di Costanzo L, Drury JE, Penning TM, Christianson DW J Biol Chem. 2008 Jun 13;283(24):16830-9. Epub 2008 Apr 11. PMID:18407998<ref>PMID:18407998</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3buv" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18407998}}, adds the Publication Abstract to the page
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*[[Aldo-keto reductase 3D structures|Aldo-keto reductase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18407998 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18407998}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3BUV is a 2 chains structure of sequences 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=3BUV OCA].
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==Reference==
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<ref group="xtra">PMID:18407998</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Christianson, D W.]]
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[[Category: Large Structures]]
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[[Category: Costanzo, L Di.]]
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[[Category: Christianson DW]]
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[[Category: Drury, J.]]
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[[Category: Di Costanzo L]]
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[[Category: Penning, T M.]]
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[[Category: Drury J]]
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[[Category: 5-beta-reductase]]
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[[Category: Penning TM]]
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[[Category: Bile acid catabolism]]
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[[Category: Catalytic tetrad]]
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[[Category: Cytoplasm]]
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[[Category: Disease mutation]]
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[[Category: E120]]
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[[Category: Hepe]]
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[[Category: Lipid metabolism]]
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[[Category: Nadp]]
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[[Category: Oxidoreductase]]
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[[Category: Steroid metabolism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 18:56:04 2009''
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Current revision

Crystal structure of human Delta(4)-3-ketosteroid 5-beta-reductase in complex with NADP and HEPES. Resolution: 1.35 A.

PDB ID 3buv

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