Structural and functional studies of enzymes involved in glycosaminoglycan synthesis and degradation

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This proposal aims at a structural and functional characterization of enzymes involved in synthesis and degradation of glycosaminoglycans (GAGs). GAGs are negatively charged linear polysaccharides that are essential for providing resilience to connective tissues, storage of growth factors and other proteins, participate in tissue repair and signaling through receptors. The presence of GAGs is usually associated with higher organisms; however, they are not unique to eukaryotes. Several specialized microorganisms also produce unsulfated forms of these polymers. Mammalian GAGs undergo rapid turnover through action of hydrolases. Bacteria evolved enzymes that use a lytic mechanism to degrade GAGs, namely polysaccharide lyases. These enzymes help bacteria to gain access to mammalian cells by degrading the surface polysaccharides or to utilize GAGs as a food source.