How ligands affect gastric H,K-ATPase activity and tegoprazan inhibition
Author Information
Author(s): Cerf Nicole T., Zerbetto de Palma Gerardo, Fedosova Natalya U., Filomatori Claudia V., Rossi Rolando C., Faraj Santiago E., Montes Mónica R.
Primary Institution: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) – Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas “Prof. Alejandro C. Paladini” (IQUIFIB), Buenos Aires, Argentina
Hypothesis
This work investigates how ligands modulate the activity of gastric H,K-ATPase and its inhibition by tegoprazan.
Conclusion
The study provides insights into the interactions between H,K-ATPase and tegoprazan, which could inform the design of new potassium-competitive acid blockers.
Supporting Evidence
- The study describes a ping-pong mechanism for H,K-ATPase activity.
- Tegoprazan binds to two different intermediate states of H,K-ATPase.
- Protonation of tegoprazan affects its binding affinity.
- K+ concentration influences the inhibition of H,K-ATPase by tegoprazan.
- Molecular dynamics simulations reveal structural changes in tegoprazan binding.
Takeaway
This research looks at how certain substances can change how a stomach enzyme works and how a drug called tegoprazan can stop it from working.
Methodology
The study used functional and structural analyses, including kinetic evaluations and molecular dynamics simulations.
Statistical Information
P-Value
0.56 ± 0.04 and 2.70 ± 0.24 at pH 7.2
Digital Object Identifier (DOI)
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