3O1D

Structure-function study of Gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097.

Summary for 3O1D

• Entry DOI: 10.2210/pdb3o1d/pdb
• Related: 2HC4 2HCD 3O1E
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 2, (1R,3R,7E,17beta)-17-[(1S)-6,6,6-trifluoro-5-hydroxy-1-(4-hydroxy-4-methylpentyl)-5-(trifluoromethyl)hex-3-yn-1-yl]-9,10-secoestra-5,7-diene-1,3-diol, ... (4 entities in total)
• Functional Keywords: transcription factor, vitamin d, nucleus, transcription-transcription activator complex, transcription/transcription activator
• Biological source: Danio rerio (leopard danio,zebra danio,zebra fish); More
• Cellular location: Nucleus: Q9PTN2 Q15596
• Total number of polymer chains: 2
• Total formula weight: 36235.21

Authors

Huet, T.,Moras, D.,Rochel, N. (deposition date: 2010-07-21, release date: 2011-07-06, Last modification date: 2024-02-21)

Primary citation

Huet, T.,Maehr, H.,Lee, H.J.,Uskokovic, M.R.,Suh, N.,Moras, D.,Rochel, N.
Structure-function study of gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097.
Medchemcomm, 2:424-429, 2011

PubMed Abstract: Derivatives of vitamin D(3) containing a second side-chain emanating at C-20 are known as gemini and act as vitamin D receptor agonists. Recently, two of these, namely Gemini-0072 and the epimeric Gemini-0097, were selected for further studies in view of their high biological activities and lack of hypercalcemic effects. We now show that the two analogs recruit coactivator SRC-1 better than the parental gemini and act as VDR superagonists. The crystal structures of complexes of zVDR with Gemini-0072 and Gemini-0097 indicate that these ligands induce an extra cavity within the ligand-binding pocket similar to gemini and that their superagonistic activity is due to an increased stabilization of helix H12.

PubMed: 22180837
DOI: 10.1039/C1MD00059D

Experimental method

X-RAY DIFFRACTION (2.4007 Å)