Crystal structure of the vitamin D nuclear receptor ligand binding domain in complex with a locked side chain analog of calcitriol.
The crystal structures of vitamin D nuclear receptor (VDR) have revealed that all compounds are anchored by the same residues to the ligand binding pocket (LBP). Based on this observation, a synthetic analog with a locked side chain (21-nor-calcitriol-20(22),23-diyne) has been synthesized in order to gain in entropy energy with a predefined active side chain conformation. The crystal structure of VDR LBD bound to this locked side chain analogue while confirming the docking provides a structural basis for the activity of this compound.
Rochel
Natacha
N
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département de Biologie et de Génomique Structurales, Illkirch F-67400, France.
Hourai
Shinji
S
Pérez-García
Xenxo
X
Rumbo
Antonio
A
Mourino
Antonio
A
Moras
Dino
D
D001665:Binding Sites; D002117:Calcitriol / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D019277:Entropy; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol