Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications.
Nuclear receptors are members of a large family of ligand-inducible transcription factors that regulate gene programs underlying a plethora of (patho)physiological phenomena. The recent determination of the crystal structures of nuclear receptor ligand-binding domains has provided an extremely detailed insight into the intra- and intermolecular mechanisms that constitute the initial events of receptor activation and signal transduction. Here, a comprehensive mechanistic view of agonist and antagonist action will be presented. Furthermore, the novel class of partial agonists-antagonists will be described and the multiple challenges and novel perspectives for nuclear-receptor-based drug design will be discussed.
Bourguet
W
W
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France. bourguet@igbmc.u-strasbg.fr
Germain
P
P
Gronemeyer
H
H
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D004965:Estrogen Antagonists / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*
D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D005938:Glucocorticoids; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear