@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 {950,
	title = {Identification and mechanism of a bacterial hydrolyzing UDP-N-acetylglucosamine 2-epimerase},
	journal = {Biochemistry},
	volume = {43},
	number = {44},
	year = {2004},
	note = {ISI Document Delivery No.: 868UVTimes Cited: 13Cited Reference Count: 38},
	month = {Nov},
	pages = {14290-14298},
	type = {Article},
	abstract = {This paper reports the first identification of a fully functional hydrolyzing UDP-N-acetylglucosamine 2-epimerase from a bacterial source. The epimerase (known as SiaA or NeuC from Neisseria meningitidis MC58 group B is shown to catalyze the conversion of UDP-GlcNAc into ManNAc and UDP in the first step of sialic acid (N-acetylneuraminic acid) biosynthesis. The mechanism is proposed to involve an anti elimination of UDP to form 2-acetamidoglucal as an intermediate, followed by the syn addition of water. The observation that the alpha-anomer of ManNAc is the true product and that solvent deuterium is incorporated at C-2 is consistent with this mechanism. The use of the O-18-labeled substrate confirms that the overall hydrolysis reaction proceeds via cleavage of the C-O bond. Furthermore, the putative intermediate 2-acetamidoglucal is shown to serve as a catalytically competent substrate and is enzymatically hydrated to give ManNAc exclusively. Isotope effect studies show that cleavage of the C-H bond is not rate limiting during catalysis. Mutagenesis studies show that three active site carboxylate residues are crucial for catalysis. In two of the mutants that were studied (E122Q and D131N), 2-acetamidoglucal was released from the active site during catalysis, providing direct evidence that the enzyme is capable of catalyzing the anti elimination of UDP from UDP-GlcNAc.},
	keywords = {2-EPIMERASE/N-ACETYLMANNOSAMINE, biosynthesis, CELL-INTERACTIONS, ENZYME, ESCHERICHIA-COLI K1, KINASE, POLYSIALIC ACID, PURIFICATION, RAT-LIVER, SIALIC-ACID, STEREOCHEMISTRY},
	isbn = {0006-2960},
	url = {<Go to ISI>://000224939400045},
	author = {Murkin, A. S. and Chou, W. K. and Wakarchuk, W. W. and Tanner, M. E.}
}
