Investigation of the effects of Lethal Toxin Neutralizing Factor (LTNF) on Insulin Degrading Enzyme (IDE) activity

WCU Author/Contributor (non-WCU co-authors, if there are any, appear on document)
Samantha Nicole Varner (Creator)
Western Carolina University (WCU )
Web Site:
Robert Youker

Abstract: Lethal Toxin Neutralizing Factor (LTNF) is a protein found in the blood stream of the Virginia opossum (Didelphis virginiana). LTNF confers immunity against toxins and venom from many organisms including different species of plants, animals, and bacteria. LTNF has been widely studied as a universal antivenom, but some of its other possible clinical applications have not yet been fully investigated. A small ten amino acid sequence of LTNF – called LT10 – has been shown to reduce Immunoglobulin E (IgE) antibody levels which are a type of antibody that has a role in allergies and autoimmune diseases such as Diabetes mellites, Grave’s disease and Hodgkin’s disease. Diabetes Mellitus is a disease that effects millions of people worldwide and prevents a person’s body from properly regulating blood glucose levels. Insulin Degrading Enzyme (IDE) is a key regulator for controlling insulin levels in the body and modulation of its activity is a promising drug target for the treatment of diabetes. LT10’s ability to regulate IgE levels suggests the possibility that it could be used to help treat some of these autoimmune diseases. Computational docking studies predict that LT10 can bind with Insulin Degrading Enzyme (IDE) and inhibit its activity, allowing it to be a possible treatment for diabetes. The overall goal for this research is to determine if LT10 can experimentally bind to IDE and affect the level of IDE activity. Results showed that when LT10 was incubated with IDE transfected lysate there was little to no inhibition and the effect was not consistent. When LT10 was incubated with purified enzyme there was a greater amount of inhibition at lower concentrations than at higher concentrations creating a U-shape response curve. This U-shape response curve suggests LT10 may be binding to multiple sites on IDE.

Additional Information

Language: English
Date: 2021
Virginia opossum
Natural immunity

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