Journal of Molecular Biology, 2010, Vol.397(1), pp.341-351
An α-2,8-linked polysialic acid (polySia) capsule confers immune tolerance to neuroinvasive, pathogenic prokaryotes such as K1 and and supports host infection by means of molecular mimicry. Bacteriophages of the K1 family, infecting K1, specifically recognize and degrade this polySia capsule utilizing tailspike endosialidases. While the crystal structure for the catalytic domain of the endosialidase of bacteriophage K1F (endoNF) has been solved, there is yet no structural information on the mode of polySia binding and cleavage available. The crystal structure of activity deficient active-site mutants of the homotrimeric endoNF cocrystallized with oligomeric sialic acid identified three independent polySia binding sites in each endoNF monomer. The bound oligomeric sialic acid displays distinct conformations at each site. In the active site, a Sia molecule is bound in an extended conformation representing the enzyme–product complex. Structural and biochemical data supported by molecular modeling enable to propose a reaction mechanism for polySia cleavage by endoNF.
Polysialic Acid ; Endonf ; Glycosidase ; Host Recognition ; Biology ; Chemistry
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