5avl

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of LXRalpha in complex with tert-butyl benzoate analog, compound 32b

Structural highlights

5avl is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NR1H3_HUMAN Orphan receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity).

Publication Abstract from PubMed

To obtain potent liver X receptor (LXR) agonists, a structure-activity relationship study was performed on a series of tert-butyl benzoate analogs. As the crystal structure analysis suggested applicable interactions between the LXR ligand-binding domain and the ligands, two key functional groups were introduced. The introduction of the hydroxyl group on the C6-position of the benzoate part enhanced the agonistic activity in a cell-based assay, and the carboxyl group in terminal improved the pharmacokinetic profile in mice, respectively. The obtained compound 32b increased blood ABCA1 mRNA expression without plasma TG elevation in both mice and cynomolgus monkeys.

Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists.,Matsui Y, Yamaguchi T, Yamazaki T, Yoshida M, Arai M, Terasaka N, Honzumi S, Wakabayashi K, Hayashi S, Nakai D, Hanzawa H, Tamaki K Bioorg Med Chem Lett. 2015 Sep 15;25(18):3914-20. doi:, 10.1016/j.bmcl.2015.07.047. Epub 2015 Jul 23. PMID:26238323^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Matsui Y, Yamaguchi T, Yamazaki T, Yoshida M, Arai M, Terasaka N, Honzumi S, Wakabayashi K, Hayashi S, Nakai D, Hanzawa H, Tamaki K. Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists. Bioorg Med Chem Lett. 2015 Sep 15;25(18):3914-20. doi:, 10.1016/j.bmcl.2015.07.047. Epub 2015 Jul 23. PMID:26238323 doi:http://dx.doi.org/10.1016/j.bmcl.2015.07.047

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5avl"

Categories: Homo sapiens | Large Structures | Hanzawa H | Matsui Y | Tamaki K

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5avl]] 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=5AVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AVL FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4KQ:2-[4-[4-[[2-[(2-METHYLPROPAN-2-YL)OXYCARBONYL]-3-OXIDANYL-4-(TRIFLUOROMETHYL)PHENYL]METHOXY]PHENYL]PHENYL]ETHANOIC+ACID'>4KQ</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4KQ:2-[4-[4-[[2-[(2-METHYLPROPAN-2-YL)OXYCARBONYL]-3-OXIDANYL-4-(TRIFLUOROMETHYL)PHENYL]METHOXY]PHENYL]PHENYL]ETHANOIC+ACID'>4KQ</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=5avl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5avl OCA], [https://pdbe.org/5avl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5avl RCSB], [https://www.ebi.ac.uk/pdbsum/5avl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5avl ProSAT]</span></td></tr>
 </table>

5avl

From Proteopedia

Current revision

Crystal structure of LXRalpha in complex with tert-butyl benzoate analog, compound 32b

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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