6P2B
Tethered PXR-LBD/SRC-1p bound to Garcinoic Acid
Summary for 6P2B
| Entry DOI | 10.2210/pdb6p2b/pdb |
| Descriptor | Nuclear receptor subfamily 1 group I member 2, (2Z,6E,10E)-13-[(2R)-6-hydroxy-2,8-dimethyl-3,4-dihydro-2H-1-benzopyran-2-yl]-2,6,10-trimethyltrideca-2,6,10-trienoic acid, DIMETHYL SULFOXIDE, ... (4 entities in total) |
| Functional Keywords | garcinoic acid, nuclear receptor, transcription |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 79455.65 |
| Authors | Walton, W.G.,Pellock, S.J.,Redinbo, M.R. (deposition date: 2019-05-21, release date: 2020-04-01, Last modification date: 2023-10-11) |
| Primary citation | Bartolini, D.,De Franco, F.,Torquato, P.,Marinelli, R.,Cerra, B.,Ronchetti, R.,Schon, A.,Fallarino, F.,De Luca, A.,Bellezza, G.,Ferri, I.,Sidoni, A.,Walton, W.G.,Pellock, S.J.,Redinbo, M.R.,Mani, S.,Pellicciari, R.,Gioiello, A.,Galli, F. Garcinoic Acid Is a Natural and Selective Agonist of Pregnane X Receptor. J.Med.Chem., 63:3701-3712, 2020 Cited by PubMed Abstract: Pregnane X receptor (PXR) is a master xenobiotic-sensing transcription factor and a validated target for immune and inflammatory diseases. The identification of chemical probes to investigate the therapeutic relevance of the receptor is still highly desired. In fact, currently available PXR ligands are not highly selective and can exhibit toxicity and/or potential off-target effects. In this study, we have identified garcinoic acid as a selective and efficient PXR agonist. The properties of this natural molecule as a specific PXR agonist were demonstrated by the screening on a panel of nuclear receptors, the assessment of the physical and thermodynamic binding affinity, and the determination of the PXR-garcinoic acid complex crystal structure. Cytotoxicity, transcriptional, and functional properties were investigated in human liver cells, and compound activity and target engagement were confirmed in vivo in mouse liver and gut tissue. In conclusion, garcinoic acid is a selective natural agonist of PXR and a promising lead compound toward the development of new PXR-regulating modulators. PubMed: 32160459DOI: 10.1021/acs.jmedchem.0c00012 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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