6S5K
LXRbeta ligand binding domain in complex with small molecule inhibitors
Summary for 6S5K
| Entry DOI | 10.2210/pdb6s5k/pdb |
| Descriptor | Oxysterols receptor LXR-beta, 3-(4-phenylbutylamino)-1,4-bis(phenylmethyl)pyrrole-2,5-dione (3 entities in total) |
| Functional Keywords | liver x receptor beta, lxrb, lxr beta, nuclear hormone receptor, receptor ligand binding domain, nuclear protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 28696.02 |
| Authors | Petersen, J. (deposition date: 2019-07-01, release date: 2019-12-18, Last modification date: 2024-05-15) |
| Primary citation | Belorusova, A.Y.,Evertsson, E.,Hovdal, D.,Sandmark, J.,Bratt, E.,Maxvall, I.,Schulman, I.G.,Akerblad, P.,Lindstedt, E.L. Structural analysis identifies an escape route from the adverse lipogenic effects of liver X receptor ligands. Commun Biol, 2:431-431, 2019 Cited by PubMed Abstract: Liver X receptors (LXRs) are attractive drug targets for cardiovascular disease treatment due to their role in regulating cholesterol homeostasis and immunity. The anti-atherogenic properties of LXRs have prompted development of synthetic ligands, but these cause major adverse effects-such as increased lipogenesis-which are challenging to dissect from their beneficial activities. Here we show that LXR compounds displaying diverse functional responses in animal models induce distinct receptor conformations. Combination of hydrogen/deuterium exchange mass spectrometry and multivariate analysis allowed identification of LXR regions differentially correlating with anti-atherogenic and lipogenic activities of ligands. We show that lipogenic compounds stabilize active states of LXRα and LXRβ while the anti-atherogenic expression of the cholesterol transporter ABCA1 is associated with the ligand-induced stabilization of LXRα helix 3. Our data indicates that avoiding ligand interaction with the activation helix 12 while engaging helix 3 may provide directions for development of ligands with improved therapeutic profiles. PubMed: 31799433DOI: 10.1038/s42003-019-0675-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
Download full validation report
