3AUR

Crystal structure of the human vitamin D receptor ligand binding domain complexed with Yne-diene type analog of active 14-epi-2beta-methyl-19-norvitamin D3

Summary for 3AUR

• Entry DOI: 10.2210/pdb3aur/pdb
• Related: 3AUQ
• Descriptor: Vitamin D3 receptor, (1R,2S,3R)-5-[2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methyl-heptan-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethynyl]-2-methyl-cyclohex-4-ene-1,3-diol (3 entities in total)
• Functional Keywords: hormone receptor, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P11473
• Total number of polymer chains: 1
• Total formula weight: 30219.96

Authors

Kakuda, S.,Takimoto-Kamimura, M. (deposition date: 2011-02-15, release date: 2011-09-14, Last modification date: 2023-11-01)

Primary citation

Sawada, D.,Tsukuda, Y.,Saito, H.,Kakuda, S.,Takimoto-Kamimura, M.,Ochiai, E.,Takenouchi, K.,Kittaka, A.
Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor
J.Am.Chem.Soc., 133:7215-7221, 2011

PubMed Abstract: In the study of the synthesis of 14-epi-19-norprevitamin D(3), we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19-nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1α,25(OH)(2)D(3).

PubMed: 21500802
DOI: 10.1021/ja201481j

Experimental method

X-RAY DIFFRACTION (2.21 Å)