Article
Replacing the eleven native tryptophans by directed evolution produces an active P-glycoprotein with site-specific, non-conservative substitutions.
Scientific reports - 21 Feb 2020
Swartz Douglas J, Singh Anukriti, Sok Narong, Thomas Joshua N, Weber Joachim, Urbatsch Ina L
Abstract excerpt
P-glycoprotein (Pgp) pumps an array of hydrophobic compounds out of cells, and has major roles in drug pharmacokinetics and cancer multidrug resistance. Yet, polyspecific drug binding and ATP hydrolysis-driven drug export in Pgp are poorly understood. Fluorescence spectroscopy using tryptophans (Trp) inserted at strategic positions is an important tool to study ligand binding. In Pgp, this method will require...
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