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New page: left|200px<br /><applet load="1xse" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xse, resolution 2.50Å" /> '''Crystal Structure of...
 
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[[Image:1xse.gif|left|200px]]<br /><applet load="1xse" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1xse, resolution 2.50&Aring;" />
'''Crystal Structure of Guinea Pig 11beta-Hydroxysteroid Dehydrogenase Type 1'''<br />


==Overview==
==Crystal Structure of Guinea Pig 11beta-Hydroxysteroid Dehydrogenase Type 1==
The metabolic reduction of 11-keto groups in glucocorticoid steroids such, as cortisone leads to the nuclear receptor ligand cortisol. This, conversion is an example of pre-receptor regulation and constitutes a, novel pharmacological target for the treatment of metabolic disorders such, as insulin resistance and possibly other derangements observed in the, metabolic syndrome, such as hyperlipidemia, hypertension, and lowered, insulin secretion. This reaction is carried out by the NADPH-dependent, type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), an enzyme, attached through an integral N-terminal transmembrane helix to the lipid, bilayer and located with its active site within the lumen of the, endoplasmic reticulum. Here we report the crystal structure of recombinant, guinea pig 11beta-HSD1. This variant was determined in complex with NADP, at 2.5 A resolution and crystallized in the presence of detergent and, guanidinium hydrochloride. The overall structure of guinea pig 11beta-HSD1, shows a clear relationship to other members of the superfamily of, short-chain dehydrogenases/reductases but harbors a unique C-terminal, helical segment that fulfills three essential functions and accordingly is, involved in subunit interactions, contributes to active site architecture, and is necessary for lipid-membrane interactions. The structure provides a, model for enzyme-lipid bilayer interactions and suggests a funneling of, lipophilic substrates such as steroid hormones from the hydrophobic, membrane environment to the enzyme active site.
<StructureSection load='1xse' size='340' side='right'caption='[[1xse]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xse]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XSE 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=1xse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xse OCA], [https://pdbe.org/1xse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xse RCSB], [https://www.ebi.ac.uk/pdbsum/1xse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xse ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DHI1_CAVPO DHI1_CAVPO] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).<ref>PMID:10699594</ref>
== 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/xs/1xse_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=1xse ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1XSE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus] with NDP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XSE OCA].
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
 
== References ==
==Reference==
<references/>
The crystal structure of guinea pig 11beta-hydroxysteroid dehydrogenase type 1 provides a model for enzyme-lipid bilayer interactions., Ogg D, Elleby B, Norstrom C, Stefansson K, Abrahmsen L, Oppermann U, Svensson S, J Biol Chem. 2005 Feb 4;280(5):3789-94. Epub 2004 Nov 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15542590 15542590]
__TOC__
[[Category: 11-beta-hydroxysteroid dehydrogenase]]
</StructureSection>
[[Category: Cavia porcellus]]
[[Category: Cavia porcellus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Abrahmsen, L.]]
[[Category: Abrahmsen L]]
[[Category: Elleby, B.]]
[[Category: Elleby B]]
[[Category: Norstrom, C.]]
[[Category: Norstrom C]]
[[Category: Ogg, D.]]
[[Category: Ogg D]]
[[Category: Oppermann, U.]]
[[Category: Oppermann U]]
[[Category: Stefansson, K.]]
[[Category: Stefansson K]]
[[Category: Svensson, S.]]
[[Category: Svensson S]]
[[Category: NDP]]
[[Category: 11beta-hydroxysteroid dehydrogenase dimer]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:18:55 2007''

Latest revision as of 13:36, 13 March 2024

Crystal Structure of Guinea Pig 11beta-Hydroxysteroid Dehydrogenase Type 1

1xse, resolution 2.50Å

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