Dimers and Trimers of Chondroitin in Molecular Docking of Bovine Testicular Hyaluronidase

Abstract

Molecular docking of a 3D model of bovine testicular hyaluronidase was performed with dimers and trimers of chondroitin. On the molecular surface of a hyaluronidase globule, eight sites for ligand binding were established. Sites 6, 3, and 1 of the enzyme structure were found to be the most important sites since chondroitin binding therewith distorts the protein 3D structure. The interactions of enzyme structure with chondroitin ligands are mainly determined by electrostatic forces. For free hyaluronidase molecule (without ligands) at temperatures above 300 K conformational transfers leading to the enzyme inactivation were noted. The inactivation was mainly manifested through irreversible attraction of the protein fragment surrounding the Glu-105 residue and the one between Arg-59 and Arg-96, where a temperature decrease did not induce the restoration of the initial view of 3D structure of the enzyme molecule. Binding of chondroitin ligands to the enzyme structure at positions 6, 3, and 1 increased its denaturation temperature by approximately 10 degrees. The most significant effect of enzyme structure stabilization was provided by chondroitin ligand binding with hyaluronidase at site 6. This effect of protein structure stabilization exceeded the one of chondroitin sulfate trimers against the enzyme inhibition by heparin tetramers, which required binding of four to five chondroitin sulfate ligands on the molecular surface of the enzyme.