Acivicin (AT125, U42126): Isolation and structure of an alkali-induced contaminant.

Martin, David G.; Mizsak, S. A.; Nielsen, James W.

doi:10.7164/antibiotics.39.603

Cited by 5 publications

(2 citation statements)

References 4 publications

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“…All of the glutamine amidotransferases possess an essential cysteine residue that initiates an attack on the amide carbonyl of glutamine to form a covalent ␥-glutamyl thioester intermediate. Acivicin contains a 4,5-dihydroisoxazole ring substituted with a chloride that is readily displaced (21)(22)(23). The activated thiolate anion of the essential cysteine residue within the amidotransferase family of enzymes has been shown with some of these enzymes to covalently react with the dihydroisoxazole ring of acivicin, resulting in irreversible inactivation.…”

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confidence: 99%

Inactivation of the Amidotransferase Activity of Carbamoyl Phosphate Synthetase by the Antibiotic Acivicin

Miles¹,

Thoden²,

Holden³

et al. 2002

Journal of Biological Chemistry

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Carbamoyl phosphate synthetase (CPS) from Escherichia coli catalyzes the formation of carbamoyl phosphate from 2 mol of ATP, bicarbonate, and glutamine. CPS was inactivated by the glutamine analog, acivicin. In the presence of ATP and bicarbonate the second-order rate constant for the inactivation of the glutamine-dependent activities was 4.0 x 10(4) m(-1) s(-1). In the absence of ATP and bicarbonate the second-order rate constant for inactivation of CPS was reduced by a factor of 200. The enzyme was protected against inactivation by the inclusion of glutamine in the reaction mixture. The ammonia-dependent activities were unaffected by the incubation of CPS with acivicin. These results are consistent with the covalent labeling of the glutamine-binding site located within the small amidotransferase subunit. The binding of ATP and bicarbonate to the large subunit of CPS must also induce a conformational change within the amidotransferase domain of the small subunit that enhances the nucleophilic character of the thiol group required for glutamine hydrolysis. The acivicin-inhibited enzyme was crystallized, and the three-dimensional structure was determined by x-ray diffraction techniques. The thiol group of Cys-269 was covalently attached to the dihydroisoxazole ring of acivicin with the displacement of a chloride ion.

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confidence: 99%

Inactivation of the Amidotransferase Activity of Carbamoyl Phosphate Synthetase by the Antibiotic Acivicin

Miles¹,

Thoden²,

Holden³

et al. 2002

Journal of Biological Chemistry

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“…Countercurrent chromatography (CCC) based on the principle of liquid-liquid partition provides a number of distinct advantages, particularly in dealing with crude natural products (21,22). We have successfuEy appUed the high-speed CCC system in the separation of plant alkaloids, plant indole hormones, and herbicides.…”

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confidence: 99%

Application of countercurrent chromatography/thermospray mass spectrometry for the identification of bioactive lignans from plant natural products

Lee¹,

Voyksner²,

Pack³

et al. 1990

Anal. Chem.

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The versatility and resolving power of countercurrent chromatography (CCC) has been demonstrated with a newly developed analytical high-speed planet centrifuge system. Interfacing countercurrent chromatography with mass spectrometry (MS) provides a new analytical methodology that integrates the advantages of countercurrent chromatography with the low detection limit and identification capability of mass spectrometry. In this paper the capability of thermospray CCC/MS is demonstrated in identifying and validating the bioactive and structurally known lignans from a crude extract of Schisandra rubriflora Rhed et Wils, a traditional Chinese herbal medicine for treatment of hepatitis.

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Chapter 1 Countercurrent Chromatography

McAlpine

Hochlowski

1989

Separation Methods for Antimicrobials, Antivirals and Enzyme Inhibitors

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Acivicin (AT125, U42126): Isolation and structure of an alkali-induced contaminant.

Cited by 5 publications

References 4 publications

Inactivation of the Amidotransferase Activity of Carbamoyl Phosphate Synthetase by the Antibiotic Acivicin

Inactivation of the Amidotransferase Activity of Carbamoyl Phosphate Synthetase by the Antibiotic Acivicin

Application of countercurrent chromatography/thermospray mass spectrometry for the identification of bioactive lignans from plant natural products

Chapter 1 Countercurrent Chromatography

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