Liver X receptor

From Proteopedia

Human liver X receptor β ligand binding domain (deepskyblue) complex with retinoic X receptor β (green) and modulator (PDB code 5kya) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function Liver X receptors (LXR) are ligand-activated transcription factors of the nuclear receptor family. There are two LXR isoforms α and β which form heterodimers with retinoic X receptor upon activation and bind to the LXR response element found in the promoter region of the target genes[1]. LXR is a lipogenic transcription factor[2]. LXRs modulate the expression of genes in cholesterol and lipid metabolism in response to changes in cellular cholesterol status. See also Intracellular receptors Disease Treatment of mice demonstrating Wilson disease with LXR agonist reduced disease manifestations without worsening neurological symptoms associated with the conventional therapy based on copper chelation[3]. Relevance LXRs have emerged as promising drug targets for anti-atherosclerotic therapies[4]. Structural highlights . LXR in the LXR/retinoic X receptor β heterodimer in a hydrophobic [5].

3D Structures of liver X receptor

Updated on 12-January-2023

References

1. ↑ Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol. 2008 Dec;59 Suppl 7:31-55. PMID:19258656
2. ↑ Cha JY, Repa JJ. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem. 2007 Jan 5;282(1):743-51. doi: 10.1074/jbc.M605023200. Epub 2006 Nov, 14. PMID:17107947 doi:http://dx.doi.org/10.1074/jbc.M605023200
3. ↑ Hamilton JP, Koganti L, Muchenditsi A, Pendyala VS, Huso D, Hankin J, Murphy RC, Huster D, Merle U, Mangels C, Yang N, Potter JJ, Mezey E, Lutsenko S. Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(-/-) (Wilson disease) mice. Hepatology. 2016 Jun;63(6):1828-41. doi: 10.1002/hep.28406. Epub 2016 Feb 22. PMID:26679751 doi:http://dx.doi.org/10.1002/hep.28406
4. ↑ Oosterveer MH, Grefhorst A, Groen AK, Kuipers F. The liver X receptor: control of cellular lipid homeostasis and beyond Implications for drug design. Prog Lipid Res. 2010 Oct;49(4):343-52. doi: 10.1016/j.plipres.2010.03.002. Epub, 2010 Apr 2. PMID:20363253 doi:http://dx.doi.org/10.1016/j.plipres.2010.03.002
5. ↑ Tice CM, Noto PB, Fan KY, Zhao W, Lotesta SD, Dong C, Marcus AP, Zheng YJ, Chen G, Wu Z, Van Orden R, Zhou J, Bukhtiyarov Y, Zhao Y, Lipinski K, Howard L, Guo J, Kandpal G, Meng S, Hardy A, Krosky P, Gregg RE, Leftheris K, McKeever BM, Singh SB, Lala D, McGeehan GM, Zhuang L, Claremon DA. Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core. Bioorg Med Chem Lett. 2016 Aug 29. pii: S0960-894X(16)30921-0. doi:, 10.1016/j.bmcl.2016.08.089. PMID:27599745 doi:http://dx.doi.org/10.1016/j.bmcl.2016.08.089