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2HAR

Crystal structure of VDR LBD in complex with 2 alpha-(3-hydroxy-1-propoxy) calcitriol

Summary for 2HAR
Entry DOI10.2210/pdb2har/pdb
Related1DB1 1IE8 1IE9 1S0Z 1S19 1TXI 2HAM 2HAS 2HB7 2HB8
DescriptorVitamin D3 receptor, 2ALPHA-(3-HYDROXYPROPOXY)-1ALPHA,25-DIHYDROXYVITAMIN D3 (3 entities in total)
Functional Keywordsalpha helical sandwich, gene regulation
Biological sourceHomo sapiens (human)
More
Cellular locationNucleus: P11473
Total number of polymer chains1
Total formula weight30296.06
Authors
Hourai, S.,Rochel, N.,Moras, D. (deposition date: 2006-06-13, release date: 2006-08-29, Last modification date: 2023-10-25)
Primary citationHourai, S.,Fujishima, T.,Kittaka, A.,Suhara, Y.,Takayama, H.,Rochel, N.,Moras, D.
Probing a Water Channel near the A-Ring of Receptor-Bound 1alpha,25-Dihydroxyvitamin D3 with Selected 2alpha-Substituted Analogues
J.Med.Chem., 49:5199-5205, 2006
Cited by
PubMed Abstract: The crystal structure of the vitamin D receptor (VDR) in complex with 1 alpha,25(OH)2D3 revealed the presence of several water molecules near the A-ring linking the ligand C-2 position to the protein surface. Here, we report the crystal structures of the human VDR ligand binding domain bound to selected C-2 alpha substituted analogues, namely, methyl, propyl, propoxy, hydroxypropyl, and hydroxypropoxy. These specific replacements do not modify the structure of the protein or the ligand, but with the exception of the methyl substituent, all analogues affect the presence and/or the location of the above water molecules. The integrity of the channel interactions and specific C-2 alpha analogue directed additional interactions correlate with the binding affinity of the ligands. In contrast, the resulting loss or gain of H-bonds does not reflect the magnitude of HL60 cell differentiation. Our overall findings highlight a rational approach to the design of more potent ligands by building in features revealed in the crystal structures.
PubMed: 16913708
DOI: 10.1021/jm0604070
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.9 Å)
Structure validation

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