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We hypothesize that (i) the slow inhibition observed in the biochemical assay with the recombinant protein with some of the compounds is due to their preferential binding to a slowly populated conformer of the NADP + -TGR(H) complex and (ii) this conformer is already populated in the worm cell interior accounting for the more rapid inhibition of TGR observed in ex vivo worms with the slow inhibitors

Furthermore, significant accumulation of TZ in the brain following administration indicates its ability to cross the bloodbrain barrier, highlighting its considerable promise for PD treatment [183]

Glutathione-mediated reversibility of covalent modification of ubiquitin carboxyl-terminal hydrolase L1 by 1,2-naphthoquinone through Cys152, but not Lys4

Images of human body and cells was created using Microsoft Copilot AI

Predicted aligned error plots (top) and predicted LDDT (local distance difference test) plots (bottom) of human (left) and yeast (right) AlphaFold models

doi: 10.1016/j.ese.2022.100205 5 AbdelfattahA.HossainA