3VJT

Vitamin D receptor complex with a carborane compound

Summary for 3VJT

• Entry DOI: 10.2210/pdb3vjt/pdb
• Related: 3VJS
• Descriptor: Vitamin D3 receptor, peptide from Mediator of RNA polymerase II transcription subunit 1, 1-(2-[(R)-2,4-Dihydroxybutoxy]ethyl)-12-(5-ethyl-5-hydroxyheptyl)-1,12-dicarba-closo-dodecaborane, ... (4 entities in total)
• Functional Keywords: nuclear receptor, synthetic agonist, carborane, transcription
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Nucleus: P13053 Q15648
• Total number of polymer chains: 2
• Total formula weight: 32584.56

Authors

Fujii, S.,Masuno, M.,Kagechika, H.,Nakabayashi, M.,Ito, N. (deposition date: 2011-10-31, release date: 2012-02-08, Last modification date: 2023-11-08)

Primary citation

Fujii, S.,Masuno, H.,Taoda, Y.,Kano, A.,Wongmayura, A.,Nakabayashi, M.,Ito, N.,Shimizu, M.,Kawachi, E.,Hirano, T.,Endo, Y.,Tanatani, A.,Kagechika, H.
Boron Cluster-based Development of Potent Nonsecosteroidal Vitamin D Receptor Ligands: Direct Observation of Hydrophobic Interaction between Protein Surface and Carborane
J.Am.Chem.Soc., 133:20933-20941, 2011

PubMed Abstract: We report here the design and synthesis of a novel vitamin D receptor (VDR) agonist whose hydrophobic core structure is p-carborane (1,12-dicarba-closo-dodecaborane, an icosahedral carbon-containing boron cluster having remarkable thermal and chemical stability and a characteristically hydrophobic B-H surface). This carborane-based VDR ligand exhibited moderate vitamin D activity, comparable to that of the natural hormone, despite its simple and flexible structure. X-ray structure analysis provided direct evidence that the carborane cage binds to the hydrophobic surface of the ligand-binding pocket of the receptor, promoting transition to the active conformation. These results indicate that the spherical B-H surface of carborane can function efficiently as a hydrophobic anchor in binding to the receptor surface, thereby allowing induced fitting of the three essential hydroxyl groups on the alkyl chains to the appropriate positions for interaction with the VDR binding site, despite the entropic disadvantage of the flexible structure. We suggest that carborane structure is a promising option in the design of novel drug candidates.

PubMed: 22066785
DOI: 10.1021/ja208797n

Experimental method

X-RAY DIFFRACTION (2 Å)