对于真菌脂肪酸合成的整体调节
S M Naimul Hasan1, Elnaz Khalili Samani1, Alexander F A Keszei2
1Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada.
棕醇-CoA通过与远端部位结合,全osterically 抑制真菌脂肪酸合成酶 (FASs),揭示了一个新的抗真菌药物标. 这一发现揭示了真菌中新脂肪酸合成的调节.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 类脂肪酸合成酶 (FASs) 对于生产和脂肪酸至关重要.
- FAS是有吸引力的抗真菌药物点,但缺乏有效的抑制剂.
- 目前尚不清楚真菌新生脂肪酸合成的调节.
研究的目的:
- 为了研究真菌FAS的全精调节.
- 确定新的脂肪酸合成的调节机制.
- 为了发现抗真菌药物设计的潜在目标.
主要方法:
- 生物化学试验用于研究酶动力学.
- 来自Saccharomyces cerevisiae和Candida albicans的真菌FAS的结构分析.
- 研究棕甲基A与FAS的结合.
主要成果:
- 帕尔米托伊尔-CoA被确定为FAS酸降解反应的全抑制剂.
- 棕甲基CoA的palmitate部分与真菌FAS的中心轮的远端部位结合.
- 棕醇-CoA的结合通过灭中央磁盘中的动力学来抑制酸缩酶 (KR) 活性.
结论:
- 菌的FAS活性由棕醇-CoA通过一种全oster机制来调节.
- 这种调节机制涉及通过热效应稳定酶.
- 已确定的全性调节为抗真菌药物开发提供了一个新的策略.
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