Structural evidence for substrate assisted catalytic mechanism of bee venom hyaluronidase, a major allergen of bee venom

摘要

Bee venom hyaluronidase (Hya) is a hydrolase which specifically cleaves the beta-1,4 glycosidic bond of hyaluronic acid (HA) in the cell surface of skin. HA is the most abundant glycosaminoglycan of the vertebrate extracellular spaces and is found invirtually all tissues and body fluids. It is a high molecular weight linear polymer built from repeating disaccharide units D-glucuronic acid(beta-1,3)-N-acetyl-D-glucosamine(beta-1,4) (GlcA-GlcNAc), Figure 1. At physiological conditions HA is a large,charged and extended polysaccharide which is exceptionally hydrophilic. The ability to bind large amounts of water confers to HA solution special viscoelastic properties which are the basis of its structural role as a stabilizer, joint lubricant and shock absorbent. Highly hydratecl HA also promotes cell locomotion and migration which are very prominent in embryogenesis, wound healing and malignancy, processes characterized by rapid increase of HA.