6k9h: Difference between revisions
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==Human LXR-beta in complex with an agonist== | |||
<StructureSection load='6k9h' size='340' side='right'caption='[[6k9h]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6k9h]] 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=6K9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K9H 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D40:~{tert}-butyl+(2~{S},3~{S})-2-oxidanylidene-2-phenyl-spiro[1~{H}-indole-3,3-pyrrolidine]-1-carboxylate'>D40</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=6k9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k9h OCA], [https://pdbe.org/6k9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k9h RCSB], [https://www.ebi.ac.uk/pdbsum/6k9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k9h ProSAT]</span></td></tr> | |||
</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> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6k9h" style="background-color:#fffaf0;"></div> | ||
[[Category: Zhang | |||
==See Also== | |||
*[[Liver X receptor|Liver X receptor]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Zhang Z]] | |||
[[Category: Zhou H]] | |||
