4ITE

Crystal structure of the human vitamin D receptor ligand binding domain complexed with 1alpha,25-Dihydroxy-2alpha-[2-(2H-tetrazol-2-yl)ethyl]vitamin D3

Summary for 4ITE

• Entry DOI: 10.2210/pdb4ite/pdb
• Related: 4ITF
• Descriptor: Vitamin D3 receptor, (1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methyl-6-oxidanyl-heptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-2-[2-(1,2,3,4-tetrazol-2-yl)ethyl]cyclohexane-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: 30318.07

Authors

Kakuda, S.,Takimoto-Kamimura, M. (deposition date: 2013-01-18, release date: 2014-01-22, Last modification date: 2023-11-08)

Primary citation

Matsuo, M.,Hasegawa, A.,Takano, M.,Saito, H.,Kakuda, S.,Chida, T.,Takagi, K.,Ochiai, E.,Horie, K.,Harada, Y.,Takimoto-Kamimura, M.,Takenouchi, K.,Sawada, D.,Kittaka, A.
Synthesis of 2 alpha-heteroarylalkyl active vitamin d3 with therapeutic effect on enhancing bone mineral density in vivo
ACS MED.CHEM.LETT., 4:671-674, 2013

PubMed Abstract: 2α-Heteroarylethyl-1α,25-dihydroxyvitamin D3 analogues, which were designed to form a hydrogen bond between Arg274 of human vitamin D receptor (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2α-position, were synthesized. Among them, 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral density than those of active vitamin D3. X-ray cocrystallographic analysis of the hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the complex.

PubMed: 24900728
DOI: 10.1021/ml400098w

Experimental method

X-RAY DIFFRACTION (2.49 Å)