Crystal structures of a family 8 polysaccharide lyase reveal open and highly occluded substrate-binding cleft conformations
Résumé
Glycosaminoglycans (GAGs) are major components of animal connective tissue. Hyaluronan/hyaluronic acid (HA) and chondroitin are two common GAGs and are composed of repeating disaccharide units of D-glucuronic acid (GlcA) residues linked to either N-acetylglucosamine (GlcNAc) residues or N-acetylgalactosamine (GalNAc) residues, respectively. The chemical formulae for these GAGs are [?4)GlcA(b1 ?3)GlcNAc(b1?]n for HA and [?4)GlcA(b1?3)GalNAc (b1?]n for chondroitin. Additionally, the GalNAc residues of chondroitin can be sulfated at the C4 or C6 position, resulting in chondroitin-4-sulfate (C4S) and chondroitin-6-sulfate (C6S), respectively. Streptomyces coelicolor A3(2) is a nonpathogenic filamentous soil bacterium and is used to produce most of the world's natural antibiotics. The genome sequence of the streptomycete 1 revealed that it is a good source of GAG-degrading enzymes. It is therefore likely that S. coelicolor uses the degradation of GAGs in the connective tissue of dead animal carcasses in soil as a nutrient source. 2 GAG-degrading enzymes have also been postulated to be implicated in several bacterial infections, possibly facilitating the spread of bacteria through connective tissue. 3 Bacterial enzymatic degradation of GAGs is facilitated by polysaccharide lyases (EC 4.2.2.-). Cleavage occurs via a b-elimination mech-Grant sponsor: Royal Society.