4k26
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==4,4-Dioxo-5,6-dihydro-[1,4,3]oxathiazines, a novel class of 11 -HSD1 inhibitors for the treatment of diabetes== | |
| + | <StructureSection load='4k26' size='340' side='right'caption='[[4k26]], [[Resolution|resolution]] 2.21Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4k26]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K26 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]] 2.21Å</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>, <scene name='pdbligand=SFF:(4AS,8AR)-N-CYCLOHEXYL-4A,5,6,7,8,8A-HEXAHYDRO-4,1,2-BENZOXATHIAZIN-3-AMINE+1,1-DIOXIDE'>SFF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4k26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k26 OCA], [https://pdbe.org/4k26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k26 RCSB], [https://www.ebi.ac.uk/pdbsum/4k26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k26 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DHI1_MOUSE DHI1_MOUSE] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Racemic cis-1,1-dioxo-5,6-dihydro-[4,1,2]oxathiazine derivative 4a was isolated as an impurity in a sample of a hit from a HTS campaign on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). After separation by chiral chromatography the 4a-S, 8a-R enantiomer of compound 4a was identified as the true, potent enzyme inhibitor. The cocrystal structure of 4a with human and murine 11ss-HSD1 revealed the unique binding mode of the oxathiazine series. SAR elucidation and optimization in regard to metabolic stability led to monocyclic tetramethyloxathiazines as exemplified by compound 21g. | ||
| - | + | 1,1-Dioxo-5,6-dihydro-[4,1,2]oxathiazines, a novel class of 11ss-HSD1 inhibitors for the treatment of diabetes.,Bohme T, Engel CK, Farjot G, Gussregen S, Haack T, Tschank G, Ritter K Bioorg Med Chem Lett. 2013 Aug 15;23(16):4685-91. doi:, 10.1016/j.bmcl.2013.05.102. Epub 2013 Jun 11. PMID:23845218<ref>PMID:23845218</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4k26" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Engel CK]] | ||
| + | [[Category: Loenze P]] | ||
| + | [[Category: Schimanski-Breves S]] | ||
| + | [[Category: Vonderheyden C]] | ||
Current revision
4,4-Dioxo-5,6-dihydro-[1,4,3]oxathiazines, a novel class of 11 -HSD1 inhibitors for the treatment of diabetes
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