Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells
Isabelle R. Taylor, Victoria A. Assimon, Szu Yu Kuo, Silvia Rinaldi, Xiaokai Li, Zapporah T. Young, Giulia Morra, Keith Green, Daniel Nguyen, Hao Shao, Sylvie Garneau‐Tsodikova, Giorgio Colombo, Jason E. Gestwicki
Abstract
Dominant negative mutants are useful tools in chemical biology, but they do not mimic the action of allosteric inhibitors. We show that properly-placed tryptophan residues can sometimes be superior for this purpose.
Topics & Concepts
Allosteric regulationMutagenesisTryptophanSelectivityChemistryStereochemistryCombinatorial chemistryBiochemistryMutationGeneEnzymeAmino acidCatalysisHeat shock proteins researchComputational Drug Discovery MethodsBioactive Compounds and Antitumor Agents