View source for 1fds


==HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 COMPLEXED WITH 17-BETA-ESTRADIOL==
<StructureSection load='1fds' size='340' side='right'caption='[[1fds]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fds]] is a 1 chain structure. 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>
</td></tr><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>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span></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=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>
</table>
== Function ==
[[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. 
== 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/fd/1fds_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=1fds ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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:8805577<ref>PMID:8805577</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1fds" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: 17-beta-estradiol 17-dehydrogenase]]
[[Category: Large Structures]]
[[Category: Breton, R]]
[[Category: Fontecilla-Camps, J C]]
[[Category: Housset, D]]
[[Category: Mazza, C]]
[[Category: 17-beta-hydroxysteroid]]
[[Category: Dehydrogenase]]