Anticapsin: an active site directed inhibitor of glucosamine-6-phosphate synthetase from Candida albicans.

  • 1 January 1986
    • journal article
    • Vol. 12, 577-83
Abstract
L-beta-(2,3-epoxycyclohexanono-4)-alanine, an active fragment of the antibiotic tetaine, identical to the antimetabolite anticapsin, is a powerful inhibitor of partially purified glucosamine-6-phosphate synthetase (2-amino-2-deoxy-D-glucose-6-phosphate ketol isomerase, aminotransferring, EC 5.3.1.19) from pathogenic fungus Candida albicans. Anticapsin was demonstrated to be a competitive inhibitor of this enzyme with respect to L-glutamine and uncompetitive with respect to D-fructose-6-phosphate. Incubation of anticapsin with glucosamine-6-phosphate synthetase in the absence of glutamine led to the formation of an inactive enzyme, irreversibly modified. The inactivation obeyed saturation kinetics; the determined Kinact was 9.5 X 10(-6) M. Addition of glutamine protected the enzyme against inactivation by anticapsin. Reaction of anticapsin with the enzyme exhibited characteristics of affinity labelling of the glutamine binding site. Probably the inactivation proceeds via an alkylation of cysteine residue at the glutamine binding site.

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