@article {1279,
	title = {The enzymes of sialic acid biosynthesis},
	journal = {Bioorganic Chemistry},
	volume = {33},
	number = {3},
	year = {2005},
	note = {ISI Document Delivery No.: 931CJTimes Cited: 36Cited Reference Count: 59},
	month = {Jun},
	pages = {216-228},
	type = {Review},
	abstract = {The sialic acids are a family of nine carbon a-keto acids that play a wide variety of biological roles in nature. In mammals, they are found at the distal ends of cell surface glycoconjugates, and thus are major determinants of cellular recognition and adhesion events. In certain strains of pathogenic bacteria, they are found in capsular polysaccharides that mask the organism from the immune system by mimicking the exterior of a mammalian cell. This review outlines recent developments in the understanding of the two main enzymes responsible for the biosynthesis of the sialic acid, N-acetylneuraminic acid. The first, a hydrolyzing UDP-N-acetyl-glucosamine 2-epimerase, generates N-acetylmannosamine and UDP from UDP-N-acetylglucosamine. The second, sialic acid synthase, generates either N-acetylneuraminic acid (bacteria) or N-acetylneuraminic acid 9-phosphate (mammals) in a condensation reaction with phosphoenolpyruvate. An emphasis is placed on an understanding of the mechanistic and structural features of these enzymes. (c) 2005 Elsevier Inc. All rights reserved.},
	keywords = {2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE, BIFUNCTIONAL KEY ENZYME, biosynthesis, ESCHERICHIA-COLI K1, FIRST 2, KDO8P SYNTHASE, MECHANISM, N-ACETYLGLUCOSAMINE 2-EPIMERASE, N-acetylmannosamine, N-ACETYLNEURAMINIC ACID, NEISSERIA-MENINGITIDIS, PHOSPHATE, phosphoenolpyruvate, RAT-LIVER, sialic acid synthase, STEPS, SYNTHASE GENE, UDP-GlcNAc 2-epimerase},
	isbn = {0045-2068},
	url = {<Go to ISI>://000229463100007},
	author = {Tanner, M. E.}
}
@article {1084,
	title = {Identification and characterization of NeuB3 from Campylobacter jejuni as a pseudaminic acid synthase},
	journal = {Journal of Biological Chemistry},
	volume = {280},
	number = {43},
	year = {2005},
	note = {ISI Document Delivery No.: 976IMTimes Cited: 22Cited Reference Count: 43},
	month = {Oct},
	pages = {35922-35928},
	type = {Article},
	abstract = {Campylobacter jejuni and Campylobacter coli are the main causes of bacterial diarrhea worldwide, and Helicobacter pylori is known to cause duodenal ulcers. In all of these pathogenic organisms, the flagellin proteins are heavily glycosylated with a 2-keto-3-deoxy acid, pseudaminic acid (5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L- manno-nonulosonic acid). The presence of pseudaminic acid is required for the proper development of the flagella and is thereby necessary for motility in, and invasion of, the host. In this study we report the first characterization of NeuB3 from C. jejuni as a pseudaminic acid synthase; the enzyme directly responsible for the biosynthesis of pseudaminic acid. Pseudaminic acid synthase catalyzes the condensation of phosphoenolpyruvate ( PEP) with the hexose, 2,4-diacetamido-2,4,6- trideoxy-L-altrose (6-deoxy-AltdiNAc), to form pseudaminic acid and phosphate. The enzymatic activity was monitored using H-1 and P-31 NMR spectroscopy, and the product was isolated and characterized. Kinetic analysis reveals that pseudaminic acid synthase requires the presence of a divalent metal ion for catalysis and that optimal catalysis occurs at pH 7.0. A coupled enzymatic assay gave the values for k(cat) of 0.65 +/- 0.01 s(-1), KmPEP of 6.5 +/- 0.4 mu M, and K(m)6-deoxy- AltdiNAc of 9.5 +/- 0.7 mu M. A mechanistic study on pseudaminic acid synthase, using[2-O-18] PEP, shows that catalysis proceeds through a C-O bond cleavage mechanism similar to other PEP condensing synthases such as sialic acid synthase.},
	keywords = {BISUBSTRATE INHIBITOR, ESCHERICHIA-COLI, HELICOBACTER-PYLORI, KDO8P SYNTHASE, NEISSERIA-MENINGITIDIS, O-SPECIFIC POLYSACCHARIDE, PNEUMOPHILA SEROGROUP-1 LIPOPOLYSACCHARIDE, PSEUDOMONAS-AERUGINOSA, SIALIC ACIDS, SOMATIC ANTIGENS},
	isbn = {0021-9258},
	url = {<Go to ISI>://000232726900019},
	author = {Chou, W. K. and Dick, S. and Wakarchuk, W. W. and Tanner, M. E.}
}
@article {1023,
	title = {The NeuC protein of Escherichia coli K1 is a UDP N-acetylglucosamine 2-epimerase},
	journal = {Journal of Bacteriology},
	volume = {186},
	number = {3},
	year = {2004},
	note = {ISI Document Delivery No.: 766HUTimes Cited: 18Cited Reference Count: 43},
	month = {Feb},
	pages = {706-712},
	type = {Article},
	abstract = {The K1 capsule is an essential virulence determinant of Escherichia coli strains that cause meningitis in neonates. Biosynthesis and transport of the capsule, an alpha-2,8-linked polymer of sialic acid, are encoded by the 17-kb kps gene cluster. We deleted neuC, a K1 gene implicated in sialic acid synthesis, from the chromosome of EV36, a K-12-K1 hybrid, by allelic exchange. Exogenously added sialic acid restored capsule expression to the deletion strain (DeltaneuC), confirming that NeuC is necessary for sialic acid synthesis. The deduced amino acid sequence of NeuC showed similarities to those of UDP-N-acetylglucosamine (GlcNAc) 2-epimerases from both prokaryotes and eukaryotes. The NeuC homologue from serotype III Streptococcus agalactiae complements DeltaneuC. We cloned the neuC gene into an intein expression vector to facilitate purification. We demonstrated by paper chromatography that the purified neuC gene product catalyzed the formation of [2-C-14]acetamidoglucal and [N-C-14]acetylmannosamine (ManNAc) from UDP-[C-14]GlcNAc. The formation of reaction intermediate 2-acetamidoglucal with the concomitant release of UDP was confirmed by proton and phosphorus nuclear magnetic resonance spectroscopy. NeuC could not use GlcNAc as a substrate. These data suggest that neuC encodes an epimerase that catalyzes the formation of ManNAc from UDP-GlcNAc via a 2-acetamidoglucal intermediate. The unexpected release of the glucal intermediate and the extremely low rate of ManNAc formation likely were a result of the in vitro assay conditions, in which a key regulatory molecule or protein was absent.},
	keywords = {2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE, ACETYLNEURAMINIC ACID SYNTHETASE, EXPRESSION, GENE-PRODUCT, NEISSERIA-MENINGITIDIS, POLYSACCHARIDE BIOSYNTHESIS, POLYSIALIC ACID, RAT-LIVER, SEQUENCE, SIALIC-ACID},
	isbn = {0021-9193},
	url = {<Go to ISI>://000188371600014},
	author = {Vann, W. F. and Daines, D. A. and Murkin, A. S. and Tanner, M. E. and Chaffin, D. O. and Rubens, C. E. and Vionnet, J. and Silver, R. P.}
}
