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3D structure prediction, dynamic investigation and rational construction of an epitope-masked thermostable bovine hyaluronidase
Journal article   Peer reviewed

3D structure prediction, dynamic investigation and rational construction of an epitope-masked thermostable bovine hyaluronidase

Mansour Amin, Ebrahim Barzegari, Aminollah Pourshohod, Majid Zeinali and Mostafa Jamalan
International journal of biological macromolecules, Vol.187, pp.544-553
30/09/2021
DOI: https://doi.org/10.1016/j.ijbiomac.2021.07.098
PMID: 34298049

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Abstract

Chemical modification Hyaluronidase from bovine testes Surface-epitope masking
Hyaluronidase (HAase) from bovine testes (BTH) has long been used in broad pharmaceutical areas, while it is associated with drawbacks in aspects of solubility, immunogenicity and pharmacokinetics. These issues can be addressed by gaining structural insights and designing rational modifications to the enzyme structure, as proposed in this study. A 3D structural model was built for HAase and underwent 40 ns of molecular dynamic simulation to examine its thermostability under normal, melting, and extreme conditions. The enzyme activity of BTH was measured against temperature and pH by kinetic assays. The interaction of bovine HAase with HA and chondroitin was defined by molecular docking. Furthermore, immunogenic properties of the enzyme were explored by immunoinformatics. Thermal effects on bovine HAase structural model and the HAase interactions with its substrates were described. We identified some B- and T-cell epitopes and showed that the protein could be recognized by human immune receptor molecules. Epitope masking by adding polyethylene glycol (PEG) to amine groups of residues presenting on the surface of the protein structure was adopted as a surface modification to enhance pharmacological properties of BTH. Assays showed that PEGylated BTH had higher thermostability and similar activity compared to the native enzyme. •Hyaluronidase is the enzyme degrading the hyaluronic acid polymer to smaller saccharides.•Bovine testes hyaluronidase is used in broad pharmaceutical areas as dispersing factor.•Solubility and pharmacokinetics of hyaluronidase could be improved by chemical modifications.•A 3D model of hyaluronidase was built and used for rational chemical modification.•Assays indicated that PEGylated hyaluronidase shows improved pharmaceutical attributes.

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