Organic Chemistry Seminar — Ryanne Ballard

About the event

Title: A Review of Tubulin Aggregation Induced by Covalent Isopeptide Cross-linking Following Chloropyrifos Oxon Exposure

Abstract: Organophosphorus toxicants (OPs) typically cause acute toxicity by inhibiting Acetylcholinesterase (AChE) which results in a buildup of neurotransmitters within neuromuscular junctions, causing constant synaptic transmission which in the worst of cases can lead to death. Chronic illness following exposure to OPs, however, lack a defined mechanism and cannot be attributed to AChE inhibition. Recent studies indicate that OPs can result in organophosphorus adducts on vulnerable lysine and tyrosine residues, those of which in close proximity to glutamic and aspartic acid residues, result in isopeptide cross-linking and protein aggregation. While isopeptide cross-linking is becoming an accepted theory for chronic illnesses attributed to exposure of OPs, a universal mechanism has yet to be defined. This presentation will explore some of the relevant data obtained by probing OP treated tubulin via LC-MS, SDS-PAGE, Western Blots, and X-Ray crystallography. In addition, the prospect of isopeptide cross-linking, proposed mechanisms, and the impact of this covalent modification will be discussed.