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Russian Journal of Bioorganic Chemistry

, Volume 44, Issue 2, pp 165–172 | Cite as

Conformational Transitions in 3D Model of Bovine Testicular Hyaluronidase during Molecular Docking with Glycosaminoglycan Ligands

  • A. V. Maksimenko
  • R. S. Beabealashvili
Article

Abstract

In silico molecular docking of the trimer repeating unit of chondroitin sulfate (sulfated hexasaccharide) and tetramer repeating unit of heparin (sulfated octasaccharide) to the 3D model of bovine testicular hyaluronidase by the methods of computational chemistry demonstrated the presence of eight significant binding sites for these ligands (cs1–cs8). The interaction of the active site of the enzyme with the heparin ligand, which inactivates the enzyme, and the protective effect of the chondroitin sulfate ligands bound to the surface sites of the biocatalyst molecule were theoretically studied using calculation approaches. We sequentially determined binding sites for the chondroitin sulfate ligands (in positions cs2, cs4, cs7, cs8 or cs1, cs2, cs4, cs7, cs8) critical for the protein structure stabilization, whose occupancy is theoretically sufficient to prevent irreversible deformations of the enzyme molecule when the heparin ligand is introduced into the cavity of its active site. Theoretical detection of these ‘sensibility points’ on the hyaluronidase globule indicates the possibility of regulating its functioning under the binding of the glycosaminoglycan ligands that initiate the fine formation of an effective type of the surface electrostatic potential. The interaction of the glycosaminoglycan ligands with hyaluronidase is mainly determined by electrostatic forces.

Keywords

bovine testicular hyaluronidase tertiary structure glycosaminoglycan ligands chondroitin sulfate heparin docking protein surface electrostatic potential enzyme functioning regulation 

Abbreviations

3D

three-dimensional (tertiary) structure of the protein

BTH

bovine testicular hyaluronidase

GAG

glycosaminoglycan

HA

hyaluronan

CHS

chondroitin sulfate

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Institute of Experimental CardiologyNational Medical Research Center for CardiologyMoscowRussia

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