A review on structural mechanisms of protein-persistent organic pollutant (POP) interactions

With the advent of the industrial revolution, the accumulation of persistent organic pollutants (POPs) in the envi-ronment has become ubiquitous. POPs are halogen-containing organic molecules that accumulate, and remain in the environment for a long time, thus causing toxic effects in living organisms. POPs exhibit a high affinity towards biological macromolecules such as nucleic acids, proteins and lipids, causing genotoxicity and impairment of ho-meostasis in living organisms. Proteins are essential members of the biological assembly, as they stipulate all necessary processes for the survival of an organism. Owing to their stereochemical features, POPs and their metabolites form energetically favourable complexes with proteins, as supported by biological and dose-dependent toxicological studies. Although individual studies have reported the biological aspects of protein-POP interactions, no compre-hensive study summarizing the structural mechanisms, thermodynamics and kinetics of protein-POP complexes is available. The current review identifies and classifies protein-POP interaction according to the structural and func-tional basis of proteins into five major protein targets, including digestive and other enzymes, serum proteins, tran-scription factors, transporters, and G-protein coupled receptors. Further, analysis detailing the molecular interactions and structural mechanism evidenced that H-bonds, van der Waals, and hydrophobic interactions essentially mediate the formation of protein-POP complexes. Moreover, interaction of POPs alters the protein conformation through kinetic and thermodynamic processes like competitive inhibition and allostery to modulate the cellular signalling processes, resulting in various pathological conditions such as cancers and inflammations. In summary, the review provides a comprehensive insight into the critical structural/molecular aspects of protein-POP interactions.

Automated summary

With the industrial revolution, the accumulation of persistent organic pollutants (POPs) in the environment has become common. These POPs, which are organic molecules containing halogens, have a high affinity for biological macromolecules such as nucleic acids, proteins, and lipids, leading to toxic effects in living organisms. This review provides a comprehensive understanding of the structural and molecular aspects of protein-POP interactions, identifying five major protein targets and highlighting the role of H-bonds, van der Waals, and hydrophobic interactions in the formation of protein-POP complexes. The interaction between POPs and proteins can alter protein conformation and modulate cellular signaling processes, ultimately leading to various pathological conditions.