STRUCTURE AND FUNCTION OF ENZYMES INVOLVED IN THE METABOLISM OF POLYSIALIC ACID

聚唾液酸是几种细菌致病的毒力因子

Polysialic acid is a virulence factor for several bacteria causing meningitis. It is also present in the developing human brain. This common occurrence along with the poor immunogenicity of this polysaccharide hampers its use as a vaccine. Several enzymes required for the biosynthesis of polysialic acid are also required for sialylation of vertebrate glycoproteins. The objective of this project is to characterize the structure and function of these enzymes and the use of them as tools for understanding sialylation in bacteria and humans. Comparison of the amino acid sequence with the E. coli CMP-sialic acid synthetase, an essential enzyme in sialylation, with sequences of the enzyme present in other pathogenic bacteria suggest conserved amino acids. Several basic residues have been identified by site directed mutagenesis as active residue in the E. coli CMP-sialic acid synthetase. Kinetic analysis suggests these residues may play a role in the interaction of nucleotide substrate.