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Updated: May 31, 2026
09:49
Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
Published on: April 2, 2015
How pH and sulfation shape human heparanase structure, stability, and substrate recognition.
Angela Pennacchio1, Yesid Aristizabal2, José Oñate-Garzón2
1Istituto di Scienze dell'Alimentazione, CNR, Avellino, 83100, Italy.
Archives of Biochemistry and Biophysics
|May 28, 2026
Summary
Human heparanase (HPSE) activity, crucial for inflammation and metastasis, is enhanced in acidic conditions and with highly sulfated substrates. This study reveals how pH and substrate structure stabilize HPSE, impacting its physiopathological roles.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Human heparanase (HPSE) is an enzyme degrading heparan sulfate, implicated in inflammation, metastasis, and matrix remodeling.
- HPSE activity is sensitive to pH and substrate sulfation, but structural details are unclear.
Purpose of the Study:
- Investigate HPSE secondary structure, stability, and substrate recognition under varying physicochemical conditions.
- Elucidate the structural basis for pH and substrate sulfation effects on HPSE.
Main Methods:
- Fourier-transform infrared (FTIR) spectroscopy to analyze secondary structure.
- Temperature-dependent intrinsic fluorescence to assess protein stability.
- Molecular dynamics (MD) simulations to model HPSE-heparan sulfate interactions.
Main Results:
- FTIR showed acidic pH induces a compact, α-helix-rich HPSE conformation.
- Fluorescence revealed maximal HPSE stability at pH 5.0.
- MD simulations demonstrated strong ionic and hydrogen-bond interactions, with higher stability for highly sulfated heparan sulfate ligands.
Conclusions:
- Acidic pH and high substrate sulfation enhance HPSE structural stability and ligand binding.
- These physicochemical factors are key regulators of HPSE activity in physiopathological processes.
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