@article {593,
	title = {Sialic acid biosynthesis: Stereochemistry and mechanism of the reaction catalyzed by the mammalian UDP-N-acetylglucosamine 2-epimerase},
	journal = {Journal of the American Chemical Society},
	volume = {125},
	number = {9},
	year = {2003},
	note = {ISI Document Delivery No.: 649YPTimes Cited: 19Cited Reference Count: 44},
	month = {Mar},
	pages = {2455-2461},
	type = {Article},
	abstract = {The bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/ManNAc kinase, catalyzes the first two steps in the biosynthesis of the sialic acids in mammals. The epimerase domain converts UDP-GlcNAc into ManNAc and UDP. This paper demonstrates that a-ManNAc is the first formed anomer and therefore the reaction proceeds with a net retention of configuration at C-1. Studies in deuterated buffer show that solvent-derived deuterium is quantitatively incorporated into the C-2 position of the product during catalysis, but it is not incorporated into the remaining pool of substrate. This indicates that the inversion of stereochemistry is ultimately brought about by the removal and replacement of a proton at C-2 and is consistent with a two-base mechanism. Studies with O-18-labeled UDP-GlcNAc show that the anomeric oxygen of the glycosyl phosphate bond departs with the UDP product and therefore the net hydrolysis reaction involves C-O bond cleavage. Incubation of the putative intermediate, 2-acetamidoglucal, with the enzyme resulted in a slow hydration reaction to give the product, ManNAc. Additional kinetic isotope effect and positional isotope exchange (PIX) experiments address the nature of the rate-determining step of the reaction and show that C-H bond cleavage is not rate limiting. Overall, these results support a reaction mechanism involving an anti-elimination of UDP to give 2-acetamidoglucal, followed by a syn-addition of water.},
	keywords = {2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE, BIFUNCTIONAL ENZYME CATALYZES, BINDING, CELL-SURFACE SIALYLATION, EPIMERIZATION, FIRST 2 STEPS, GLUTAMATE RACEMASE, POSITIONAL ISOTOPE EXCHANGE, RAT-LIVER},
	isbn = {0002-7863},
	url = {<Go to ISI>://000181235800030},
	author = {Chou, W. K. and Hinderlich, S. and Reutter, W. and Tanner, M. E.}
}
@article {454,
	title = {Dehydroalanine-based inhibition of a peptide epimerase from spider venom},
	journal = {Journal of Organic Chemistry},
	volume = {67},
	number = {24},
	year = {2002},
	note = {ISI Document Delivery No.: 620AATimes Cited: 17Cited Reference Count: 42},
	month = {Nov},
	pages = {8389-8394},
	type = {Article},
	abstract = {Ribosomally produced peptides that contain D-amino acids have been isolated from a number of vertebrate and invertebrate sources. In each case, the D-amino acids are introduced by a posttranslational modification of a parent peptide containing only amino acids of the L-configuration. The only known enzyme to catalyze such a reaction is the peptide epimerase (also known as peptide isomerase) from the venom of the funnel web spider, Agelenopsis aperta. This enzyme interconverts two 48-amino-acid-long peptide toxins that differ only by the stereochemistry at a single serine residue. In this paper we report the synthesis and testing of two pentapeptide analogues that contain modified amino acids at the site normally occupied by the substrate serine residue. When the L-chloroalanine-containing peptide 3 was incubated with the epimerase it was converted into the dehydroalanine-containing peptide 4 via an elimination of HCl. The dehydroalanine peptide 4 was independently synthesized and found to act as a potent inhibitor of the epimerase (IC50 = 0.5 muM). These results support a direct deprotonation/reprotonation mechanism in which a carbanionic intermediate is formed. The observed inhibition by 4 can be attributed to the sp(2)-hybridization of the a-carbon in the dehydroalanine unit that mimics the planar geometry of the anionic intermediate.},
	keywords = {ACID, ACTIVE-SITE, ENZYME, GLUTAMATE RACEMASE, GRAMICIDIN-S SYNTHETASE, INFLUENZAE DIAMINOPIMELATE EPIMERASE, INITIATION MODULE PHEATE, MECHANISM, PROLINE RACEMASE, RESIDUES},
	isbn = {0022-3263},
	url = {<Go to ISI>://000179509400011},
	author = {Murkin, A. S. and Tanner, M. E.}
}
@article {520,
	title = {Understanding nature{\textquoteright}s strategies for enzyme-catalyzed racemization and epimerization},
	journal = {Accounts of Chemical Research},
	volume = {35},
	number = {4},
	year = {2002},
	note = {ISI Document Delivery No.: 544TBTimes Cited: 65Cited Reference Count: 36},
	month = {Apr},
	pages = {237-246},
	type = {Review},
	abstract = {Epimerases and racemases are enzymes that catalyze the inversion of stereochemistry in biological molecules. In this article, three distinct examples are used to illustrate the wide range of chemical strategies employed during catalysis, and the diverse set of ancestors from which these enzymes have evolved. Glutamate racemase is an example of an enzyme that operates at an "activated" stereocenter (bearing a relatively acidic proton) and employs a nonstereospecific deprotonation/reprotonation mechanism. UDP-N-Acetylglucosamine 2-epimerase acts at an "unactivated" stereocenter and uses a mechanism involving a nonstereospecific elimination/addition of UDP. L-Ribulose phosphate 4-epimerase also acts at an unactivated stereocenter and uses a nonstereospecific retroaldol/aldol mechanism.},
	keywords = {ALDOLASE, CLASS-II, ESCHERICHIA-COLI, GLUTAMATE RACEMASE, IDENTIFICATION, L-FUCULOSE-1-PHOSPHATE, L-RIBULOSE-5-PHOSPHATE 4-EPIMERASE, MECHANISM, N-ACETYLGLUCOSAMINE 2-EPIMERASE, PHOSPHATE, RESIDUES},
	isbn = {0001-4842},
	url = {<Go to ISI>://000175175800005},
	author = {Tanner, M. E.}
}
