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6k9g
From Proteopedia
(Difference between revisions)
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==Human LXR-beta in complex with an agonist== | ==Human LXR-beta in complex with an agonist== | ||
| - | <StructureSection load='6k9g' size='340' side='right'caption='[[6k9g]]' scene=''> | + | <StructureSection load='6k9g' size='340' side='right'caption='[[6k9g]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K9G OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6k9g]] 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=6K9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K9G FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D3R:~{tert}-butyl+(2~{R},3~{R})-2-[3-[4-(hydroxymethyl)-3-methylsulfonyl-phenyl]phenyl]-2-oxidanylidene-spiro[1~{H}-indole-3,3-pyrrolidine]-1-carboxylate'>D3R</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=6k9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k9g OCA], [https://pdbe.org/6k9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k9g RCSB], [https://www.ebi.ac.uk/pdbsum/6k9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k9g ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Discovery and optimization of selective liver X receptor beta (LXRbeta) agonists are challenging due to the high homology of LXRalpha and LXRbeta in the ligand-binding domain. There is only one different residue (Val versus Ile) at the ligand-binding pocket of LXRs. With machine learning methods, we identified pan LXR agonists with a novel scaffold (spiro[pyrrolidine-3,3'-oxindole]). Then, we figured out the mechanism of LXR isoform selectivity from co-crystal structures. Based on the mechanism and the new scaffold, LXRbeta selective agonists were designed and synthesized. This led to the discovery of LXRbeta agonists 4-7rr, 4-13 and 4-13rr with IC50 values ranging from 1.78 to 6.36 muM against glioblastoma in vitro. Treatment with 50 mg/kg/day of 4-13 for 15 days significantly reduced tumor growth using an in vivo xenograft glioblastoma model. | ||
| + | |||
| + | Discovery of new LXRbeta agonists as glioblastoma inhibitors.,Chen H, Chen Z, Zhang Z, Li Y, Zhang S, Jiang F, Wei J, Ding P, Zhou H, Gu Q, Xu J Eur J Med Chem. 2020 May 15;194:112240. doi: 10.1016/j.ejmech.2020.112240. Epub, 2020 Mar 17. PMID:32248003<ref>PMID:32248003</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6k9g" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Liver X receptor|Liver X receptor]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Zhang Z]] | [[Category: Zhang Z]] | ||
[[Category: Zhou H]] | [[Category: Zhou H]] | ||
Current revision
Human LXR-beta in complex with an agonist
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