6s4t
From Proteopedia
(Difference between revisions)
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<StructureSection load='6s4t' size='340' side='right'caption='[[6s4t]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='6s4t' size='340' side='right'caption='[[6s4t]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6s4t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S4T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6s4t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S4T FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KVB:2-[4-[[3-[3-(phenylmethyl)-8-(trifluoromethyl)quinolin-4-yl]phenoxy]methyl]phenyl]ethanoic+acid'>KVB</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KVB:2-[4-[[3-[3-(phenylmethyl)-8-(trifluoromethyl)quinolin-4-yl]phenoxy]methyl]phenyl]ethanoic+acid'>KVB</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1H2, LXRB, NER, UNR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6s4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s4t OCA], [http://pdbe.org/6s4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s4t RCSB], [http://www.ebi.ac.uk/pdbsum/6s4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s4t ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6s4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s4t OCA], [http://pdbe.org/6s4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s4t RCSB], [http://www.ebi.ac.uk/pdbsum/6s4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s4t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://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). | [[http://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 == | ||
| + | Liver X receptors (LXRs) are attractive drug targets for cardiovascular disease treatment due to their role in regulating cholesterol homeostasis and immunity. The anti-atherogenic properties of LXRs have prompted development of synthetic ligands, but these cause major adverse effects-such as increased lipogenesis-which are challenging to dissect from their beneficial activities. Here we show that LXR compounds displaying diverse functional responses in animal models induce distinct receptor conformations. Combination of hydrogen/deuterium exchange mass spectrometry and multivariate analysis allowed identification of LXR regions differentially correlating with anti-atherogenic and lipogenic activities of ligands. We show that lipogenic compounds stabilize active states of LXRalpha and LXRbeta while the anti-atherogenic expression of the cholesterol transporter ABCA1 is associated with the ligand-induced stabilization of LXRalpha helix 3. Our data indicates that avoiding ligand interaction with the activation helix 12 while engaging helix 3 may provide directions for development of ligands with improved therapeutic profiles. | ||
| + | |||
| + | Structural analysis identifies an escape route from the adverse lipogenic effects of liver X receptor ligands.,Belorusova AY, Evertsson E, Hovdal D, Sandmark J, Bratt E, Maxvall I, Schulman IG, Akerblad P, Lindstedt EL Commun Biol. 2019 Nov 22;2:431. doi: 10.1038/s42003-019-0675-0. eCollection 2019. PMID:31799433<ref>PMID:31799433</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6s4t" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Jansson, A]] | [[Category: Jansson, A]] | ||
Current revision
LXRbeta ligand binding domain in comlpex with small molecule inhibitors
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