Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation
Shaffer, Hally A.
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Nuclear receptors are ligand-activated transcription factors that play significant roles in various biological processes within the body, such as cell development, hormone metabolism, reproduction, and cardiac function. As transcription factors, nuclear receptors are involved in many diseases, such as diabetes, cancer, and arthritis, resulting in approximately 10-15% of the pharmaceutical drugs presently on the market being targeted toward nuclear receptors. Structurally, nuclear receptors consist of a DNA-binding domain (DBD), responsible for binding specific sequences of DNA called response elements, fused to a ligand-binding domain (LBD) through a hinge region. The LBD binds a small molecule ligand. Upon ligand binding, the LBD changes to an active conformation leading to the recruitment of coactivator (CoAC) proteins and initiation of transcription. As a result of their involvement in disease, there is an emphasis on engineering nuclear receptors for applications in gene therapy, drug discovery and metabolic engineering.
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Mitchel, Jonathan EvanWe developed a microarray data analytical method capable of identifying ligand-activated nuclear receptors (NRs) in samples of the MCF7 cell line that are cultured among uncharacterized ligands. Principally, we applied ...
Engineering a better receptor: characterization of retinoid x receptor alpha and functional variants Watt, Terry J. (Georgia Institute of Technology, 2007-11-14)The human retinoid X receptor alpha (hRXRalpha) is a member of the nuclear receptor super-family of ligand-activated transcription factors. The Doyle laboratory has previously engineered a variety of functional hRXRalpha ...
A mannose receptor-like molecule likely serves as the mate recognition pheromone receptor in the male rotifer Brachionus manjavacas Couser, Laura M. (Georgia Institute of Technology, 2010-05-12)Mate recognition in the male rotifer Brachionus manjavacas is controlled by contact chemoreception, which occurs when the male has a head-on encounter with a conspecific female. The female expresses a glycoprotein, the ...