Molecular Insight into the Inhibitory Effect of Sulfated Polysaccharide Fucoidan on Hyaluronidase Activity

Area of Science:

• Biochemistry
• Enzymology
• Natural Products Chemistry

Background:

• Hyaluronic acid (HA) is crucial for water retention and osmoregulation in vivo.
• Hyaluronidase enzymes degrade HA, impacting physiological functions.
• Fucoidan, a sulfated polysaccharide from brown algae, is explored for its biological activities.

Purpose of the Study:

• To investigate the inhibitory effect of fucoidan on bovine testicular hyaluronidase activity.
• To determine the mechanism and binding affinity of fucoidan to hyaluronidase.

Main Methods:

• Purification of bovine testicular hyaluronidase.
• Enzyme inhibition assays to determine IC50 values.
• Molecular docking and molecular dynamics simulations.
• Ramachandran plot analysis for structural changes.

Main Results:

• Fucoidan demonstrated strong competitive inhibition of hyaluronidase with an IC50 of 4.137 μM.
• Molecular docking revealed fucoidan binding to the hyaluronidase active site via hydrogen bonds and hydrophobic interactions.
• Molecular dynamics simulations indicated a stable fucoidan-hyaluronidase complex (binding energy: -24.59 kcal/mol).
• Structural analysis showed fucoidan binding induces a more inert and compact active site.

Conclusions:

• Fucoidan is a potent competitive inhibitor of hyaluronidase.
• The binding is stable and involves specific interactions at the enzyme's active site.
• Fucoidan's inhibitory action suggests potential applications in preserving hyaluronic acid levels.