3d3e

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{{Seed}}
 
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[[Image:3d3e.png|left|200px]]
 
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==Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Benzamide Inhibitor==
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The line below this paragraph, containing "STRUCTURE_3d3e", creates the "Structure Box" on the page.
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<StructureSection load='3d3e' size='340' side='right'caption='[[3d3e]], [[Resolution|resolution]] 2.60&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'>[[3d3e]] is a 4 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=3D3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D3E 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]] 2.6&#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=D3E:N-CYCLOPROPYL-N-(TRANS-4-PYRIDIN-3-YLCYCLOHEXYL)-4-[(1S)-2,2,2-TRIFLUORO-1-HYDROXY-1-METHYLETHYL]BENZAMIDE'>D3E</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
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{{STRUCTURE_3d3e| PDB=3d3e | 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=3d3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d3e OCA], [https://pdbe.org/3d3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d3e RCSB], [https://www.ebi.ac.uk/pdbsum/3d3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d3e ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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).
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== Function ==
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[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).
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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/d3/3d3e_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=3d3e 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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We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.
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===Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Benzamide Inhibitor===
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Discovery of Novel, Potent Benzamide Inhibitors of 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model.,Julian LD, Wang Z, Bostick T, Caille S, Choi R, Degraffenreid M, Di Y, He X, Hungate RW, Jaen JC, Liu J, Monshouwer M, McMinn D, Rew Y, Sudom A, Sun D, Tu H, Ursu S, Walker N, Yan X, Ye Q, Powers JP J Med Chem. 2008 Jun 14;. PMID:18553955<ref>PMID:18553955</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 3d3e" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18553955}}, adds the Publication Abstract to the page
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*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18553955 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18553955}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3D3E 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=3D3E OCA].
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==Reference==
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Discovery of Novel, Potent Benzamide Inhibitors of 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model., Julian LD, Wang Z, Bostick T, Caille S, Choi R, Degraffenreid M, Di Y, He X, Hungate RW, Jaen JC, Liu J, Monshouwer M, McMinn D, Rew Y, Sudom A, Sun D, Tu H, Ursu S, Walker N, Yan X, Ye Q, Powers JP, J Med Chem. 2008 Jun 14;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18553955 18553955]
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[[Category: 11-beta-hydroxysteroid 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: Liu, J.]]
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[[Category: Liu J]]
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[[Category: Sudom, A.]]
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[[Category: Sudom A]]
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[[Category: Walker, N P.]]
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[[Category: Walker NP]]
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[[Category: Wang, Z.]]
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[[Category: Wang Z]]
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[[Category: 11beta]]
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[[Category: Dehydrogenase]]
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[[Category: Endoplasmic reticulum]]
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[[Category: Glycoprotein]]
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[[Category: Hydroxysteroid]]
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[[Category: Lipid metabolism]]
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[[Category: Membrane]]
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[[Category: Microsome]]
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[[Category: Nadp]]
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[[Category: Oxidoreductase]]
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[[Category: Polymorphism]]
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[[Category: Signal-anchor]]
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[[Category: Steroid metabolism]]
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[[Category: Transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 23 10:12:32 2008''
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Current revision

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Benzamide Inhibitor

PDB ID 3d3e

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