1fds

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[[Image:1fds.gif|left|200px]]
 
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==HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 COMPLEXED WITH 17-BETA-ESTRADIOL==
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The line below this paragraph, containing "STRUCTURE_1fds", creates the "Structure Box" on the page.
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<StructureSection load='1fds' size='340' side='right'caption='[[1fds]], [[Resolution|resolution]] 1.70&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'>[[1fds]] is a 1 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=1FDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FDS FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.7&#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=EST:ESTRADIOL'>EST</scene></td></tr>
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{{STRUCTURE_1fds| PDB=1fds | 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=1fds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fds OCA], [https://pdbe.org/1fds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fds RCSB], [https://www.ebi.ac.uk/pdbsum/1fds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fds ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
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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/fd/1fds_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=1fds ConSurf].
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<div style="clear:both"></div>
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'''HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 COMPLEXED WITH 17-BETA-ESTRADIOL'''
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==See Also==
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*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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BACKGROUND: The steroid hormone 17beta-estradiol is important in the genesis and development of human breast cancer. Its intracellular concentration is regulated by 17beta-hydroxysteroid dehydrogenase, which catalyzes the reversible reduction of estrone to 17beta-estradiol. This enzyme is thus an important target for inhibitor design. The precise localization and orientation of the substrate and cofactor in the active site is of paramount importance for the design of such inhibitors, and for an understanding of the catalytic mechanism. RESULTS: The structure of recombinant human 17beta-hydroxysteroid dehydrogenase of type 1 (17beta-HSD1) in complex with estradiol at room temperature has been determined at 1.7 A resolution, and a ternary 17betaHSD1-estradiol-NADP+ complex at -150 degrees C has been solved and refined at 2.20 A resolution. The structures show that estradiol interacts with the enzyme through three hydrogen bonds (involving side chains of Ser142, Tyr155 and His221), and hydrophobic interactions between the core of the steroid and nine other residues. The NADP+ molecule binds in an extended conformation, with the nicotinamide ring close to the estradiol molecule. CONCLUSIONS: From the structure of the complex of the enzyme with the substrate and cofactor of the oxidation reaction, the orientation of the substrates for the reduction reaction can be deduced with confidence. A triangular hydrogen-bond network between Tyr155, Ser142 and O17 from estradiol probably facilitates the deprotonation of the reactive tyrosine, while the conserved Lys159 appears not to be directly involved in catalysis. Both the steroid-binding site and the NADPH-binding site can be proposed as targets for the design of inhibitors.
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==About this Structure==
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1FDS 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=1FDS OCA].
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==Reference==
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The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors., Breton R, Housset D, Mazza C, Fontecilla-Camps JC, Structure. 1996 Aug 15;4(8):905-15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8805577 8805577]
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[[Category: Estradiol 17-beta-dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Breton, R.]]
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[[Category: Breton R]]
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[[Category: Fontecilla-Camps, J C.]]
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[[Category: Fontecilla-Camps J-C]]
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[[Category: Housset, D.]]
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[[Category: Housset D]]
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[[Category: Mazza, C.]]
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[[Category: Mazza C]]
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[[Category: 17-beta-hydroxysteroid]]
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[[Category: Dehydrogenase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:12:43 2008''
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Current revision

HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 COMPLEXED WITH 17-BETA-ESTRADIOL

PDB ID 1fds

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