2ilt: Difference between revisions

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New page: left|200px<br /> <applet load="2ilt" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ilt, resolution 2.300Å" /> '''Human 11-beta-Hydr...
 
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[[Image:2ilt.gif|left|200px]]<br />
<applet load="2ilt" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2ilt, resolution 2.300&Aring;" />
'''Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) with NADP and Adamantane Sulfone Inhibitor'''<br />


==Overview==
==Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) with NADP and Adamantane Sulfone Inhibitor==
Potent and selective adamantane sulfone and sulfonamide inhibitors of, 11-beta-HSD-1 have been discovered. Selected compounds from these series, have robust pharmacokinetic profiles and strongly inhibit liver, fat, and, brain HSD1 for extended periods after oral dosing.
<StructureSection load='2ilt' size='340' side='right'caption='[[2ilt]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ilt]] 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=2ILT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ILT 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=NN1:2-(2-CHLORO-4-FLUOROPHENOXY)-2-METHYL-N-[(1R,2S,3S,5S,7S)-5-(METHYLSULFONYL)-2-ADAMANTYL]PROPANAMIDE'>NN1</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=2ilt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ilt OCA], [https://pdbe.org/2ilt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ilt RCSB], [https://www.ebi.ac.uk/pdbsum/2ilt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ilt ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/DHI1_HUMAN DHI1_HUMAN] Defects in HSD11B1 are a cause of cortisone reductase deficiency (CRD) [MIM:[https://omim.org/entry/604931 604931]. In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).
== Function ==
[https://www.uniprot.org/uniprot/DHI1_HUMAN DHI1_HUMAN] 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).
== 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/il/2ilt_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=2ilt ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Cortisone reductase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600713 600713]]
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
 
__TOC__
==About this Structure==
</StructureSection>
2ILT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NI, NAP and NN1 as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2ILT OCA].
 
==Reference==
Adamantane sulfone and sulfonamide 11-beta-HSD1 Inhibitors., Sorensen B, Winn M, Rohde J, Shuai Q, Wang J, Fung S, Monzon K, Chiou W, Stolarik D, Imade H, Pan L, Deng X, Chovan L, Longenecker K, Judge R, Qin W, Brune M, Camp H, Frevert EU, Jacobson P, Link JT, Bioorg Med Chem Lett. 2007 Jan 15;17(2):527-32. Epub 2006 Oct 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17070044 17070044]
[[Category: 11-beta-hydroxysteroid dehydrogenase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Judge, R.]]
[[Category: Judge R]]
[[Category: Link, J.T.]]
[[Category: Link JT]]
[[Category: Longenecker, K.L.]]
[[Category: Longenecker KL]]
[[Category: Qin, W.]]
[[Category: Qin W]]
[[Category: Sorensen, B.]]
[[Category: Sorensen B]]
[[Category: NAP]]
[[Category: NI]]
[[Category: NN1]]
[[Category: hsd1]]
[[Category: inhibitor]]
[[Category: nadp]]
 
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Retrieved from "https://proteopedia.org/2ilt"