Modeling the Binding of Tetrodotoxin and Saxitoxin to the Nav1.7 Voltage-Gated Sodium Channel
Abstract
Approximately 1.5 billion people suffer from chronic pain, with 68 million people suffering in the U.S alone. Chronic pain is pain that persists longer than 12 weeks despite medication or treatment. Within the U.S. about 5.5 million cancer patients experience chronic pain. Around 20% of these pains have neuropathic origins and develop from radiation therapy. Halneuron, a new drug in development, seeks to provide pain relief to those suffering from chemotherapy-induced neuropathic pain. This drug includes Tetrodotoxin (TTX), a potent neurotoxin found in species of pufferfish. Our 3D-printed model displays the structural details of TTX as a pore blocker within the Nav1.7 channel. The model also shows the structural differences between TTX and a similar toxin, Saxitoxin (STX). STX is most concentrated in mussels and other shellfish that can induce paralytic shellfish poisoning. Both toxins are Nav1.7 channel pore blockers that inhibit pain. TTX and STX were chosen from the Protein Data Bank and related literature studying pain inhibition. The PDB files 6J8J and 6J8H were used to develop a 3D molecular model showing how both toxins bind to the channel and inhibit action potentials. The files were imported to Jmol, where interactions and amino acids were highlighted to display binding differences. Our model contains key features such as the alpha subunit, backbone, and alpha helices of the Nav1.7 channel. Overall, constructing this model allowed us to visualize the binding differences between TTX and STX to the Nav1.7 channel, and look into future applications regarding treatment of pain disorders.
Faculty Sponsors
Dr. Emily Schmitt Lavin, Dr. Arthur Sikora
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Modeling the Binding of Tetrodotoxin and Saxitoxin to the Nav1.7 Voltage-Gated Sodium Channel
Alvin Sherman Library
Approximately 1.5 billion people suffer from chronic pain, with 68 million people suffering in the U.S alone. Chronic pain is pain that persists longer than 12 weeks despite medication or treatment. Within the U.S. about 5.5 million cancer patients experience chronic pain. Around 20% of these pains have neuropathic origins and develop from radiation therapy. Halneuron, a new drug in development, seeks to provide pain relief to those suffering from chemotherapy-induced neuropathic pain. This drug includes Tetrodotoxin (TTX), a potent neurotoxin found in species of pufferfish. Our 3D-printed model displays the structural details of TTX as a pore blocker within the Nav1.7 channel. The model also shows the structural differences between TTX and a similar toxin, Saxitoxin (STX). STX is most concentrated in mussels and other shellfish that can induce paralytic shellfish poisoning. Both toxins are Nav1.7 channel pore blockers that inhibit pain. TTX and STX were chosen from the Protein Data Bank and related literature studying pain inhibition. The PDB files 6J8J and 6J8H were used to develop a 3D molecular model showing how both toxins bind to the channel and inhibit action potentials. The files were imported to Jmol, where interactions and amino acids were highlighted to display binding differences. Our model contains key features such as the alpha subunit, backbone, and alpha helices of the Nav1.7 channel. Overall, constructing this model allowed us to visualize the binding differences between TTX and STX to the Nav1.7 channel, and look into future applications regarding treatment of pain disorders.
