How hyaluronan - protein complexes modulate the hyaluronidase activity: The model

Jean-Claude Vincent , Hélène Lenormand

Hyaluronan (HA) is the substrate of hyaluronidase (HAase). In addition, HA is able to form electrostatic complexes with many proteins, including HAase. Experiments have shown the strong inhibition of the HA hydrolysis catalysed by HAase when performed at low HAase over HA concentration ratio and under low ionic strength conditions. Non-catalytic P proteins are able to compete with HAase to form electrostatic complexes with HA and thus to modulate HAase activity. We have modelled the HA-HAase-P system by considering the competition between the two complex equilibria HA-P and HA-HAase, the Michaelis-Menten type behaviour of HAase, and the non-activity of the electrostatically complexed HAase. Simulations performed by introducing experimental data produce a theoretical behaviour similar to the experimental one, including all the atypical phenomena observed : substrate-dependence, enzyme-dependence and protein-dependence of HAase. This shows that our assumptions are sufficient to explain the behaviour of the system and allows us to estimate unknown parameters and suggest new developments.

Mots clés: Hyaluronan; hyaluronidase; polysaccharide-protein complex; enzyme activity; modelling

Jean-Claude Vincent, Hélène Lenormand. How hyaluronan - protein complexes modulate the hyaluronidase activity: The model. Biophysical Chemistry, 2009, 145 (2-3), pp.126. ⟨10.1016/j.bpc.2009.09.010⟩. ⟨hal-00588351⟩