Webinar title: Identification of Protein Targets of Reactive Toxicants Using Chemoproteomics

Speaker: Hui Peng

Webinar time: September 19, 2024 (Thursday) 13:30

Venue: Room 200, New Environmental Building

Inviter: Kun Zhang

Abstract:

Electrophilic pollutants in the environment can cause toxicity by directly reacting chemically with the amino acid residues of human proteins. However, there are two key difficulties in the study of their toxicity: 1) How to understand the reactivity and selectivity of pollutants and proteins? 2) How to systematically identify toxic electrophilic pollutants in the environment? Taking organophosphates and halogenated disinfection byproducts as examples, we use chemical proteomics to reveal their molecular mechanisms of toxicity. We found that organophosphates can react extensively with liver proteins through synthetic chemical probes and proteomics. Among them, the binding of FABP1 with organophosphates has a strong structural selectivity for side chains and phosphate groups. For halogenated disinfection byproducts, we found through chemical proteomics that they can react extensively with cysteine residues, and their reactivity well explains the structure-effect relationship. Finally, we systematically identified a large number of unknown disinfection byproducts in drinking water through thiol chemical probes and non-targeted methods. This series of studies shows that by understanding the chemical reactivity of electrophilic pollutants with proteins, their seemingly complex molecular toxicological mechanisms can be deeply revealed. This research method is not only applicable to industrial chemicals, but more importantly, it can be used to deeply study toxic chemical components produced in real complex environments, including air pollution and drinking water disinfection.

About the speaker:

Hui Peng, Associate Professor, School of Chemistry and Environment, University of Toronto. After receiving his bachelor's and doctoral degrees from Peking University in 2008 and 2013, he completed postdoctoral research at the University of Toronto and the University of Saskatchewan, and joined the University of Toronto as a faculty member in 2017. The research group's research focuses on the interaction between proteins and small molecules: 1) Identification of exogenous and endogenous protein ligands using protein-mediated non-targeted analysis; 2) Identification of target proteins of environmental pollutants using chemical proteomics. To date, more than 100 papers have been published and he has won many awards including the Canadian Chemical Society EN Early Career Research Award (2024) and the ES&T James J. Morgan Early Career Award (2024).