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Title Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation
Publication Date
Date Accessioned
Degree PhD
Discipline/Department Chemistry and Biochemistry
Degree Level doctoral
University/Publisher Georgia Tech
Abstract 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.
Subjects/Keywords Nuclear receptors; Chemical complementation; Negative chemical complementation; Yeast-two hybrid selection; Pregnane X receptor; Estrogen receptor; Pregnane; Protein engineering; Nuclear receptors (Biochemistry); Transcription factors; Yeast Genetics
Contributors Bahareh Azizi (Committee Chair); Donald Doyle (Committee Chair); Andreas Bommarius (Committee Co-Chair); Loren Williams (Committee Co-Chair); Adegboyega Oyelere (Committee Member); Nick Hud (Committee Member); Sheldon May (Committee Member)
Country of Publication us
Record ID handle:1853/39620
Repository gatech
Date Indexed 2020-05-13
Issued Date 2011-04-05 00:00:00
Note [degree] Ph.D.; [advisor] Committee Chair: Bahareh Azizi; Committee Chair: Donald Doyle; Committee Co-Chair: Andreas Bommarius; Committee Co-Chair: Loren Williams; Committee Member: Adegboyega Oyelere; Committee Member: Nick Hud; Committee Member: Sheldon May;

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