7UW2

Crystal structure of human Retinoid X receptor alpha ligand binding domain complex with UAB116 and coactivator peptide GRIP-1

Summary for 7UW2

• Entry DOI: 10.2210/pdb7uw2/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, Nuclear receptor coactivator 2, (2E,4E,6Z,8E)-8-{3-[(2S)-butan-2-yl]-2-(3-methylbutyl)cyclohex-2-en-1-ylidene}-3,7-dimethylocta-2,4,6-trienoic acid, ... (4 entities in total)
• Functional Keywords: retinoid x receptor, retinoid x receptor alpha, ligand binding domain, coactivator complex, inhibitor complex, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 28806.47

Authors

Chattopadhyay, D.,Yang, Z.,Atigadda, V. (deposition date: 2022-05-02, release date: 2023-03-15, Last modification date: 2023-10-25)

Primary citation

Atigadda, V.R.,Kashyap, M.P.,Yang, Z.,Chattopadhyay, D.,Melo, N.,Sinha, R.,Belyaeva, O.V.,Chou, C.F.,Chang, P.L.,Kedishvili, N.Y.,Grubbs, C.J.,Renfrow, M.B.,Muccio, D.D.,Elmets, C.A.,Athar, M.
Conformationally Defined Rexinoids for the Prevention of Inflammation and Nonmelanoma Skin Cancers.
J.Med.Chem., 65:14409-14423, 2022

PubMed Abstract: Compound is a potent rexinoid that is highly effective in cancer chemoprevention but elevates serum triglycerides. In an effort to separate the lipid toxicity from the anticancer activity of , we synthesized four new analogs of rexinoid , of which three rexinoids did not elevate serum triglycerides. Rexinoids and are twice as potent as rexinoid in binding to Retinoid X receptor (RXR). retinoic acid (ATRA) plays a key role in maintaining skin homeostasis, and rexinoids are highly effective in upregulating the genes responsible for the biosynthesis of ATRA. Inflammation plays a key role in skin cancer, and rexinoids and are highly effective in diminishing LPS-induced inflammation. Rexinoids and are highly effective in preventing UVB-induced nonmelanoma skin cancer (NMSC) without displaying any overt toxicities. Biophysical studies of rexinoids and bound to hRXRα-ligand binding domain (LBD) reveal important conformational and dynamical differences in the ligand binding domain.

PubMed: 36318154
DOI: 10.1021/acs.jmedchem.2c00735

Experimental method

X-RAY DIFFRACTION (1.88 Å)