Understanding Thrombin Structure and Stability through Ligand Binding
Author Information
Author(s): Silva Vivian de Almeira, Cargnelutti Maria Thereza, Giesel Guilherme M., Palmieri Leonardo C., Monteiro Robson Q., Verli Hugo, Lima Luis Mauricio T. R.
Primary Institution: Federal University of Rio de Janeiro (UFRJ), Brazil
Hypothesis
How does ligand binding affect the conformation and stability of alpha-thrombin in solution?
Conclusion
Ligand binding to alpha-thrombin significantly alters its conformation and increases its stability against denaturation.
Supporting Evidence
- Binding of PPACK to thrombin increases its thermal stability.
- Molecular dynamics simulations show minimal structural changes upon ligand binding.
- SAXS measurements indicate similar overall shapes for free and PPACK-bound thrombin.
Takeaway
When a special molecule binds to thrombin, it helps the protein stay stable and change shape, which is important for how it works in the body.
Methodology
The study used small-angle X-ray scattering, molecular dynamics simulations, and thermodynamic measurements to analyze thrombin's structure and stability.
Limitations
The study lacks high-resolution structures of ligand-free thrombin and relies on simulations and indirect measurements.
Digital Object Identifier (DOI)
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