Milewski S, Chmara H, Borowski E
Drugs Exp Clin Res. 1986;12(6-7):577-83.
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.
L-β-(2,3-环氧环己烷酮-4)-丙氨酸是抗生素替他宁的活性片段，与抗代谢物抗荚膜素相同，是来自致病性真菌白色念珠菌的部分纯化的葡糖胺-6-磷酸合成酶（2-氨基-2-脱氧-D-葡萄糖-6-磷酸酮醇异构酶，氨基转移，EC 5.3.1.19）的强效抑制剂。已证明抗荚膜素是该酶对L-谷氨酰胺的竞争性抑制剂，对D-果糖-6-磷酸是非竞争性抑制剂。在没有谷氨酰胺的情况下，抗荚膜素与葡糖胺-6-磷酸合成酶孵育会导致形成一种不可逆修饰的无活性酶。失活遵循饱和动力学；测定的Kinact为9.5×10⁻⁶ M。添加谷氨酰胺可保护该酶免受抗荚膜素的失活作用。抗荚膜素与该酶的反应表现出对谷氨酰胺结合位点进行亲和标记的特征。失活可能是通过谷氨酰胺结合位点处半胱氨酸残基的烷基化进行的。
