Theoretical Grounding and Formation of Experimental Approaches to Hyaluronidase Structure Consolidation due to Its Computational Interactions with Shortchain Glycosaminoglycan Ligands

The computational study of 3D model hyaluronidase interaction with shortchain glycosaminoglycan ligands demonstrated the diversity and significance of their reaction on enzyme structure. It has been realized due to electrostatic noncovalent interactions (without specific coupling with active site) inducing the perceptible conformational alterations of biocatalyst molecule. As a result of this the inactivation and stabilization of enzyme globule are observed, change of inhibition of biocatalyst by heparin. The binding of chondroitin trimers (on centers cn6, cn3, cn1) to hyaluronidase molecular surface increased the enzyme stability, binding of chondroitin sulfate trimers (on centers cs2, cs4, cs7, cs8 or cs1, cs2, cs4, cs7, cs8) decreased the inhibition of enzyme by tetramer heparin. It should be noted the importance of ligand binding for regulation of enzyme functioning and existence of multiform and multicomponent microenvironment of enzyme. The sequence of preferable coupling of ligands with hyaluronidase is elicited in our study and with its help was evaluate reality of experimental selective modification of enzyme (possibly no covalently or covalently, for instance, with chondroitin sulfate trimers on centers cs7, cs1, cs5) for experimental obtaining of stabilized enzyme forms of medical destination. The perspective approaches for this aim may be the no covalent reaction on hyaluronidase by chondroitin or chondroitin sulfate trimers as well covalent modification of biocatalyst by chondroitin sulfate trimers.