7VQP

Vitamin D receptor complexed with a lithocholic acid derivative

Summary for 7VQP

• Entry DOI: 10.2210/pdb7vqp/pdb
• Descriptor: Vitamin D3 receptor, Mediator of RNA polymerase II transcription subunit 1, 3-((R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-(2-hydroxy-2-methylpropyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamido)propanoic acid, ... (4 entities in total)
• Functional Keywords: vitamin d receptor, lithocholic acid, transcription
• Biological source: Rattus norvegicus; More
• Total number of polymer chains: 2
• Total formula weight: 32669.69

Authors

Kato, K.,Numoto, N.,Kagechika, H.,Tanatani, A.,Ito, N. (deposition date: 2021-10-20, release date: 2022-03-09, Last modification date: 2023-11-29)

Primary citation

Yoshihara, A.,Kawasaki, H.,Masuno, H.,Takada, K.,Numoto, N.,Ito, N.,Hirata, N.,Kanda, Y.,Ishizawa, M.,Makishima, M.,Kagechika, H.,Tanatani, A.
Lithocholic Acid Amides as Potent Vitamin D Receptor Agonists.
Biomolecules, 12:-, 2022

PubMed Abstract: 1α,25-Dihydroxyvitamin D [1α,25(OH)D, ] is an active form of vitamin D and regulates various biological phenomena, including calcium and phosphate homeostasis, bone metabolism, and immune response via binding to and activation of vitamin D receptor (VDR). Lithocholic acid (LCA, ) was identified as a second endogenous agonist of VDR, though its potency is very low. However, the lithocholic acid derivative () is a more potent agonist than 1α,25(OH)D, (), and its carboxyl group has similar interactions to the 1,3-dihydroxyl groups of with amino acid residues in the VDR ligand-binding pocket. Here, we designed and synthesized amide derivatives of in order to clarify the role of the carboxyl group. The synthesized amide derivatives showed HL-60 cell differentiation-inducing activity with potency that depended upon the substituent on the amide nitrogen atom. Among them, the -cyanoamide is more active than either or .

PubMed: 35053278
DOI: 10.3390/biom12010130

Experimental method

X-RAY DIFFRACTION (1.94 Å)