Bioinformatic analysis of 302 reactive metabolite target proteins. Which ones are important for cell death?

ABSTRACT: Many low molecular weight compounds undergo biotransformation to chemically reactive metabolites (CRMs) that covalently modify cellular proteins. However, the mechanisms by which this covalent binding leads to cytotoxicity are not understood. Prior analyses of lists of target proteins sorted by functional categories or hit frequency have not proven informative. In an attempt to move beyond covalent binding, we hypothesized that xenobiotic posttranslational modification of proteins might disrupt important protein-protein interactions (PPIs) and thereby direct cells from homeostasis into cell death pathways. To test this hypothesis, we analyzed a list of 302 proteins (66% rat, 26% mouse, 5% human) known to be targeted by 41 different cytotoxic CRMs. Human orthologs of rodent proteins were fo

SUBMITTER: Hanzlik RP 

PROVIDER: S-EPMC3807624 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature