3FAL
humanRXR alpha & mouse LXR alpha complexed with Retenoic acid and GSK2186
Summary for 3FAL
| Entry DOI | 10.2210/pdb3fal/pdb |
| Descriptor | Retinoic acid receptor RXR-alpha, Oxysterols receptor LXR-alpha, RETINOIC ACID, ... (5 entities in total) |
| Functional Keywords | nuclear hormone receptor nonsteroidal lxr agonist choloestorol metabolism, dna-binding, host-virus interaction, metal-binding, nucleus, polymorphism, receptor, transcription, transcription regulation, ubl conjugation, zinc, zinc-finger, signaling protein |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: P19793 Nucleus (Potential): Q9Z0Y9 |
| Total number of polymer chains | 4 |
| Total formula weight | 117065.62 |
| Authors | Chao, E.Y.,Caravella, J.A.,Watson, M.A.,Campobasso, N.,Ghisletti, S.,Billin, A.N.,Galardi, C.,Willson, T.M.,Zuercher, W.J.,Collins, J.L. (deposition date: 2008-11-17, release date: 2009-04-14, Last modification date: 2023-12-27) |
| Primary citation | Chao, E.Y.,Caravella, J.A.,Watson, M.A.,Campobasso, N.,Ghisletti, S.,Billin, A.N.,Galardi, C.,Wang, P.,Laffitte, B.A.,Iannone, M.A.,Goodwin, B.J.,Nichols, J.A.,Parks, D.J.,Stewart, E.,Wiethe, R.W.,Williams, S.P.,Smallwood, A.,Pearce, K.H.,Glass, C.K.,Willson, T.M.,Zuercher, W.J.,Collins, J.L. Structure-guided design of N-phenyl tertiary amines as transrepression-selective liver X receptor modulators with anti-inflammatory activity. J.Med.Chem., 51:5758-5765, 2008 Cited by PubMed Abstract: A cocrystal structure of T1317 (3) bound to hLXRbeta was utilized in the design of a series of substituted N-phenyl tertiary amines. Profiling in binding and functional assays led to the identification of LXR modulator GSK9772 ( 20) as a high-affinity LXRbeta ligand (IC 50 = 30 nM) that shows separation of anti-inflammatory and lipogenic activities in human macrophage and liver cell lines, respectively. A cocrystal structure of the structurally related analog 19 bound to LXRbeta reveals regions within the receptor that can affect receptor modulation through ligand modification. Mechanistic studies demonstrate that 20 is greater than 10-fold selective for LXR-mediated transrepression of proinflammatory gene expression versus transactivation of lipogenic signaling pathways, thus providing an opportunity for the identification of LXR modulators with improved therapeutic indexes. PubMed: 18800767DOI: 10.1021/jm800612u PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.36 Å) |
Structure validation
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