Medina-Cleghorn_2015_Chem.Biol_22_1394

Reference

Title : Mapping Proteome-Wide Targets of Environmental Chemicals Using Reactivity-Based Chemoproteomic Platforms - Medina-Cleghorn_2015_Chem.Biol_22_1394
Author(s) : Medina-Cleghorn D , Bateman LA , Ford B , Heslin A , Fisher KJ , Dalvie ED , Nomura DK
Ref : Chemical Biology , 22 :1394 , 2015
Abstract :

We are exposed to a growing number of chemicals in our environment, most of which have not been characterized in terms of their toxicological potential or mechanisms. Here, we employ a chemoproteomic platform to map the cysteine reactivity of environmental chemicals using reactivity-based probes to mine for hyper-reactive hotspots across the proteome. We show that environmental contaminants such as monomethylarsonous acid and widely used pesticides such as chlorothalonil and chloropicrin possess common reactivity with a distinct set of proteins. Many of these proteins are involved in key metabolic processes, suggesting that these targets may be particularly sensitive to environmental electrophiles. We show that the widely used fungicide chlorothalonil specifically inhibits several metabolic enzymes involved in fatty acid metabolism and energetics, leading to dysregulated lipid metabolism in mice. Our results underscore the utility of using reactivity-based chemoproteomic platforms to uncover novel mechanistic insights into the toxicity of environmental chemicals.

PubMedSearch : Medina-Cleghorn_2015_Chem.Biol_22_1394
PubMedID: 26496688

Related information

Citations formats

Medina-Cleghorn D, Bateman LA, Ford B, Heslin A, Fisher KJ, Dalvie ED, Nomura DK (2015)
Mapping Proteome-Wide Targets of Environmental Chemicals Using Reactivity-Based Chemoproteomic Platforms
Chemical Biology 22 :1394

Medina-Cleghorn D, Bateman LA, Ford B, Heslin A, Fisher KJ, Dalvie ED, Nomura DK (2015)
Chemical Biology 22 :1394