3frj
From Proteopedia
(Difference between revisions)
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<StructureSection load='3frj' size='340' side='right'caption='[[3frj]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='3frj' size='340' side='right'caption='[[3frj]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3frj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[3frj]] is a 2 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=3FRJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FRJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A49:N-{1-[(1-CARBAMOYLCYCLOPROPYL)METHYL]PIPERIDIN-4-YL}-N-CYCLOPROPYL-4-[(1S)-2,2,2-TRIFLUORO-1-HYDROXY-1-METHYLETHYL]BENZAMIDE'>A49</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A49:N-{1-[(1-CARBAMOYLCYCLOPROPYL)METHYL]PIPERIDIN-4-YL}-N-CYCLOPROPYL-4-[(1S)-2,2,2-TRIFLUORO-1-HYDROXY-1-METHYLETHYL]BENZAMIDE'>A49</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | |
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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=3frj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3frj OCA], [https://pdbe.org/3frj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3frj RCSB], [https://www.ebi.ac.uk/pdbsum/3frj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3frj ProSAT]</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=3frj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3frj OCA], [https://pdbe.org/3frj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3frj RCSB], [https://www.ebi.ac.uk/pdbsum/3frj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3frj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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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=3frj ConSurf]. | </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=3frj ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Discovery and optimization of a piperidyl benzamide series of 11beta-HSD1 inhibitors is described. This series was derived from a cyclohexyl benzamide lead structures to address PXR selectivity, high non-specific protein binding, poor solubility, limited in vivo exposure, and in vitro cytotoxicity issues observed with the cyclohexyl benzamide structures. These efforts led to the discovery of piperidyl benzamide 15 which features improved properties over the cyclohexyl benzamide derivatives. | ||
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| - | Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11beta-HSD1 inhibitors.,Rew Y, McMinn DL, Wang Z, He X, Hungate RW, Jaen JC, Sudom A, Sun D, Tu H, Ursu S, Villemure E, Walker NP, Yan X, Ye Q, Powers JP Bioorg Med Chem Lett. 2009 Mar 15;19(6):1797-801. Epub 2009 Jan 23. PMID:19217779<ref>PMID:19217779</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3frj" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
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[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Sudom | + | [[Category: Sudom A]] |
| - | [[Category: Walker | + | [[Category: Walker NP]] |
| - | [[Category: Wang | + | [[Category: Wang Z]] |
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Current revision
Crystal Structure of 11b-Hydroxysteroid Dehydrogenase-1 (11b-HSD1) in Complex with Piperidyl Benzamide Inhibitor
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