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The liver produces high levels of thiomethyl metabolites from glutathione conjugates We then used in vitro liver models (HepaRG-HRG-and primary human hepatocytes-PHH) to provide a better understanding of the formation of these thiomethyl metabolites (in particular to identify their precursors), and a better understanding of the site where the biotransformation occurs

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The major difference is that whereas only the main chain carboxylate of wild-type Thr1273 interacts with basic Lys17 on the WD40 surface, both the side chain and main chain carboxylate groups of the clientized Glu1273 residue form extensive interactions with a WD40 basic cluster of Arg15, Lys17, and Arg272 (Fig