7VUE
Structural insight of the molecular mechanism of cilofexor bound to FXR
Summary for 7VUE
| Entry DOI | 10.2210/pdb7vue/pdb |
| Descriptor | Bile acid receptor, Peptide from Nuclear receptor coactivator 2, 2-[3-[4-[[3-[2,6-bis(chloranyl)phenyl]-5-cyclopropyl-1,2-oxazol-4-yl]methoxy]-2-chloranyl-phenyl]-3-oxidanyl-azetidin-1-yl]pyridine-4-carboxylic acid, ... (4 entities in total) |
| Functional Keywords | nuclear receptor, ligand binding, nuclear protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 28742.19 |
| Authors | Jiang, L.,Chen, Y.C. (deposition date: 2021-11-02, release date: 2022-03-16, Last modification date: 2024-11-06) |
| Primary citation | Jiang, L.,Liu, X.,Wei, H.,Dai, S.,Qu, L.,Chen, X.,Guo, M.,Chen, Y. Structural insight into the molecular mechanism of cilofexor binding to the farnesoid X receptor. Biochem.Biophys.Res.Commun., 595:1-6, 2022 Cited by PubMed Abstract: Farnesoid X receptor (FXR) is a bile acid-related nuclear receptor and is considered a promising target to treat several liver disorders. Cilofexor is a selective FXR agonist and has already entered phase III trials in primary sclerosing cholangitis (PSC) patients. Pruritis caused by cilofexor treatment is dose dependent. The binding characteristics of cilofexor with FXR and its pruritogenic mechanism remain unclear. In our research, the affinity of cilofexor bound to FXR was detected using an isothermal titration calorimetry (ITC) assay. The binding mechanism between cilofexor and FXR-LBD is explained by the cocrystal structure of the FXR/cilofexor complex. Structural models indicate the possibility that cilofexor activates Mas-related G protein-coupled receptor X4 (MRGPRX4) or G protein-coupled bile acid receptor 1 (GPBAR1), leading to pruritus. In summary, our analyses provide a molecular mechanism of cilofexor binding to FXR and provide a possible explanation for the dose-dependent pruritis of cilofexor. PubMed: 35091108DOI: 10.1016/j.bbrc.2022.01.069 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.601 Å) |
Structure validation
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