Modifying ligand specificity of gene regulatory proteins.
Nuclear receptors contain a conserved hydrophobic ligand binding pocket that is particularly amenable to structure-based protein engineering. Thus, site-directed mutagenesis of the ligand binding pocket has resulted in the creation of nuclear receptors with novel ligand specificities. Such proteins are now being used to control gene expression in vivo in a ligand-dependent manner.
Doyle
D F
DF
Departments of Pharmacology and Biochemistry, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75235-9041, USA.
Mangelsdorf
D J
DJ
Corey
D R
DR
D000818:Animals; D004440:Ecdysone / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D008024:Ligands; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D015202:Protein Engineering; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism
D004967:Estrogens; D005938:Glucocorticoids; D008024:Ligands; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D004440:Ecdysone; D011374:Progesterone; D014212:Tretinoin