抗生素corramycin采用类似β的结构,并被激酶comG失活
Sebastian Adam1, Franziska Fries1,2,3, Alexander von Tesmar1
1Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Campus E8 1, 66123 Saarbrücken, Germany.
一种新型的激酶,ComG,通过酸化使抗生素corramycin失活,从而赋予宿主耐药性. 这一发现对于开发新抗生素来对抗抗性阴性细菌至关重要.
科学领域:
- 微生物学
- 生物化学
- 结构生物学
背景情况:
- 格拉姆阴性细菌的抗生素耐药性是一个主要的公共卫生威胁.
- 了解新的抵抗机制是对抗抗性的关键.
- 科拉米辛是一种新型抗生素,有效对抗阴性病原体.
研究的目的:
- 识别和描述抗素的机制.
- 阐明ComG激酶的结构和功能.
- 评估科拉米辛作为未来抗生素的潜力.
主要方法:
- 生物化学测定用于研究激酶活性和基质特异性.
- 结晶学测定与胺复合的ComG的结构.
- 对ComG同类生物信息分析.
主要成果:
- 通过酸化,激酶ComG使康拉米失活,从而产生宿主耐药性.
- 最接近的结构亲属是氨基甘油酸转化酶,但对它们缺乏活性.
- 结构分析揭示了corramycin的β-hairpin结构以及ComG基特异性的基础.
结论:
- 它代表了抗生素耐药性的新机制.
- 科拉米辛的独特耐药性和ComG的特定活性表明交叉耐药性潜力较低.
- 科拉米辛是进一步开发抗生素的有希望的候选药物.
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