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多氧霉素D和多氧霉素对酿酒酵母几丁质合成酶1和2的差异抑制作用

Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins.

作者信息

Cabib E

机构信息

Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.

出版信息

Antimicrob Agents Chemother. 1991 Jan;35(1):170-3. doi: 10.1128/AAC.35.1.170.

Abstract

Polyoxin D, nikkomycin X, and nikkomycin Z are all competitive inhibitors of chitin synthetase 2 (Chs2), the essential enzyme for primary septum formation in Saccharomyces cerevisiae, and of Chs1, a repair enzyme. However, Chs2 is more resistant to these antibiotics than Chs1. When Co2+, the best stimulator of Chs2, was used in the assay for this enzyme, the differences in the Ki values for nikkomycins between the two isozymes reached 3 orders of magnitude. These results point to differences in the active sites of the two isozymes. Polyoxin D was much more effective than nikkomycin Z in inhibiting cell growth. This underlines the importance of the choice of enzyme and of assay conditions when cell wall-synthesizing enzymes are used in screens for possible antifungal agents.

摘要

多氧霉素D、多抗霉素X和多抗霉素Z都是几丁质合成酶2(Chs2)的竞争性抑制剂,Chs2是酿酒酵母中形成初级隔膜的必需酶,也是一种修复酶Chs1的竞争性抑制剂。然而,Chs2比Chs1对这些抗生素更具抗性。当在该酶的测定中使用Chs2的最佳刺激剂Co2+时,两种同工酶对多抗霉素的Ki值差异达到3个数量级。这些结果表明两种同工酶的活性位点存在差异。在抑制细胞生长方面,多氧霉素D比多抗霉素Z有效得多。这突出了在筛选可能的抗真菌剂时,使用细胞壁合成酶时选择酶和测定条件的重要性。

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