@article {2182,
	title = {Synthesis, characterisation, and in vitro evaluation of Pro(2)-Ile(3)-S-deoxo-amaninamide and Pro(2)-D-allo-Ile(3)-S-deoxo-amaninamide: Implications for structure-activity relationships in amanitin conformation and toxicity},
	journal = {Chemistry-a European Journal},
	volume = {14},
	number = {11},
	year = {2008},
	note = {ISI Document Delivery No.: 291XITimes Cited: 0Cited Reference Count: 39May, Jonathan P. Fournier, Pierre Patrick, Brian O. Perrin, David M.},
	pages = {3410-3417},
	type = {Article},
	abstract = {The amatoxins are a family of toxic bicyclic peptides that inhibit RNA polymerase II. Herein we discuss an improved synthesis of these compounds from easily obtainable amino acids by means of a solid-phase methodology. Interestingly, we obtained two products of the same mass following our final macrocyclisation, relating to a similar distribution of products described in some previous reports. One of these products was the desired amatoxin; Pro(2)-Ile(3)-S-deoxo-amaninamide 1b. The other compound, after thorough investigation, was confirmed to be the epimer Pro(2)-D-allo-Ile(3)-S-deoxo-amaninamide la, not an atropisomer structure as previously suggested in syntheses of related amanitin analogues. Crystallographic data of la confirms the presence of a beta II-turn, rather than a PI-turn common to the natural toxin and 1b. This difference explains the large variation in CD spectra, although it seems to have relatively little effect on the bioactivity in vitro. These data provide new insights into the bicyclic amatoxin structure.},
	keywords = {ALPHA-AMANITIN, amatoxin, atropisomerism, circular dichroism, CRYSTALLINE STATE, CYCLIZATION, CYSTEINE SULFHYDRYL-GROUPS, EPIMERIZATION, MOLECULAR-STRUCTURE, PEPTIDES, RESOLUTION, RNA-POLYMERASE-II, SERIES, TOXIN BETA-AMANITIN, transcription},
	isbn = {0947-6539},
	url = {<Go to ISI>://000255230200020},
	author = {May, J. P. and Fournier, P. and Patrick, B. O. and Perrin,David M.}
}
@article {1213,
	title = {Dismutase activity of ADP-L-glycero-D-manno-heptose 6-epimerase: Evidence for a direct oxidation/reduction mechanism},
	journal = {Biochemistry},
	volume = {44},
	number = {15},
	year = {2005},
	note = {ISI Document Delivery No.: 916ZNTimes Cited: 11Cited Reference Count: 33},
	month = {Apr},
	pages = {5907-5915},
	type = {Article},
	abstract = {The first positive evidence for the utilization of a direct C-6" oxidation/reduction mechanism by ADP-L-glycero-D-manno-heptose 6-epimerase is reported here. The epimerase (HldD or AGME, formerly RfaD) operates in the biosynthetic pathway Of L-glycero-D-manno-heptose, which is a conserved sugar in the core region of lipopolysaccharide (LPS) of Gram-negative bacteria. The stereochemical inversion catalyzed by the epimerase is interesting as it occurs at an "unactivated" stereocenter that lacks an acidic C-H bond, and therefore, a direct deprotonation/reprotonation mechanism cannot be employed. Instead, the epimerase employs a transient oxidation strategy involving a tightly bound NADP(+) cofactor. A recent study ruled out mechanisms involving transient oxidation at C-4 {\textquoteright}{\textquoteright} and C-7 {\textquoteright}{\textquoteright} and supported a mechanism that involves an initial oxidation directly at the C-6 {\textquoteright}{\textquoteright} position to generate a 6"-keto intermediate (Read, J. A., Ahmed, R. A., Morrison, J. P., Coleman, W. G., Jr., Tanner, M. E. (2004) J. Am. Chem. Soc. 126, 8878-8879). A subsequent nonstereospecific reduction of the ketone intermediate can generate either epimer of the ADP-heptose. In this work, an intermediate analogue containing an aldehyde functionality at C-6 {\textquoteright}{\textquoteright}, ADP-beta-D-manno-hexodialdose, is prepared in order to probe the ability of the enzyme to catalyze redox chemistry at this position. It is found that incubation of the aldehyde with a catalytic amount of the epimerase leads to a dismutation process in which one-half of the material is oxidized to ADP-beta-D-mannuronic acid and the other half is reduced to ADP-beta-D-mannose. Transient reduction of the enzyme-bound NADP(+) was monitored by UV spectroscopy and implicates the cofactor{\textquoteright}s involvement during catalysis.},
	keywords = {ACID, ALCOHOL-DEHYDROGENASE, ALDEHYDE DEHYDROGENASE, D-MANNOHEPTOSE 6-EPIMERASE, DROSOPHILA-MELANOGASTER, EPIMERIZATION, ESCHERICHIA-COLI, GLUCOSE DEHYDROGENASE, LIVER, SITE RESIDUES, UDP-GALACTOSE 4-EPIMERASE},
	isbn = {0006-2960},
	url = {<Go to ISI>://000228425600037},
	author = {Morrison, J. P. and Read, J. A. and Coleman, W. G. and Tanner, M. E.}
}
@article {1234,
	title = {Efficient chemoenzymatic synthesis of ADP-D-glycero-beta-D-manno-heptose and a mechanistic study of ADP-L-glycero-D-manno-heptose 6-epimerase},
	journal = {Organic Letters},
	volume = {7},
	number = {12},
	year = {2005},
	note = {ISI Document Delivery No.: 932SSTimes Cited: 10Cited Reference Count: 21},
	month = {Jun},
	pages = {2457-2460},
	type = {Article},
	abstract = {[GRAPHICS] A chemoenzymatic synthesis of ADP-D-glycero-\&beta;-D-manno-heptose (ADP-D,D-Hep) is described in which D,D-Hep 7-phosphate is converted to ADP-D,D-Hep by two biosynthetic enzymes. This strategy allows access to the 6"-deuterated analogue, which upon incubation with the epimerase showed complete retention of the isotopic label at the 6"-position. This provides evidence for a direct oxidation mechanism in which the hydride initially transferred to the NADP(+) cofactor is subsequently returned to the same carbon in a nonstereospecific manner.},
	keywords = {biosynthesis, CARBON, D-MANNOHEPTOSE 6-EPIMERASE, EPIMERIZATION, PATHWAY},
	isbn = {1523-7060},
	url = {<Go to ISI>://000229574300042},
	author = {Read, J. A. and Ahmed, R. A. and Tanner, M. E.}
}
@article {972,
	title = {Active site mutants of the "non-hydrolyzing" UDP-N-acetylglucosamine 2-epimerase from Escherichia coli},
	journal = {Biochimica Et Biophysica Acta-Proteins and Proteomics},
	volume = {1700},
	number = {1},
	year = {2004},
	note = {ISI Document Delivery No.: 833VCTimes Cited: 4Cited Reference Count: 26},
	month = {Jul},
	pages = {85-91},
	type = {Article},
	abstract = {The "non-hydrolyzing" bacterial UDP-N-acetylglucosamine 2-epimerase catalyzes the reversible interconversion of UDP-N-acetylglucosarnine (UDP-GlcNAc) and UDP-N-acetylmannosamine (UDP-ManNAc). This homodimeric enzyme is allosterically activated by its substrate, UDP-GlcNAc, and it is thought that one subunit plays a regulatory role, while that of the other plays a catalytic role. In this work, five active site mutants were prepared (D95N, E117Q, E131Q, K15A, and H213N) and analyzed in terms of their effects on binding, catalysis, and allosteric regulation. His213 appears to play a role in UDP binding and may also assist in catalysis and/or regulation, but is not a key catalytic residue. Lys15 appears to be quite important for binding. All three of the carboxylate mutants showed dramatic decreases in the value of k(cat) but relatively unaffected values of Km. Thus, these residues are playing key roles in catalysis and/or regulation. In the case of E117Q, the reaction intermediates are released into solution at a rate comparable to that of the overall catalysis. This may indicate that Glu117 plays the role as an acid/base catalyst in the second step of the UDP-GlcNAc epimerization reaction. All three carboxylate mutants were found to exhibit impaired allosteric control. (C) 2004 Elsevier B.V. All rights reserved.},
	keywords = {2-acetamidoglucal, 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE, ACID BIOSYNTHESIS, allosteric regulation, enterobacterial common antigen, EPIMERIZATION, HOMOLOGY, MECHANISM, MUTAGENESIS, RAT-LIVER, SEQUENCE, sialic acid, STREPTOCOCCUS-PNEUMONIAE, TRANSFERASES, UDP-N-acetylmannosamine},
	isbn = {1570-9639},
	url = {<Go to ISI>://000222367400011},
	author = {Samuel, J. and Tanner, M. E.}
}
@article {966,
	title = {The mechanism of the reaction catalyzed by ADP-beta-L-glycero-D-manno-heptose 6-epimerase},
	journal = {Journal of the American Chemical Society},
	volume = {126},
	number = {29},
	year = {2004},
	note = {ISI Document Delivery No.: 840JTTimes Cited: 14Cited Reference Count: 24},
	month = {Jul},
	pages = {8878-8879},
	type = {Article},
	keywords = {4, 6-DEHYDRATASE, BACTERIA, D-MANNOHEPTOSE 6-EPIMERASE, EPIMERIZATION, ESCHERICHIA-COLI, GLUCOSE, INSIGHTS, NUCLEOTIDE-MODIFYING ENZYMES, OUTER-MEMBRANE, UDP-GALACTOSE 4-EPIMERASE},
	isbn = {0002-7863},
	url = {<Go to ISI>://000222855300009},
	author = {Read, J. A. and Ahmed, R. A. and Morrison, J. P. and Coleman, W. G. and Tanner, M. E.}
}
@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.}
}
