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对DosT和DosS传感器激酶的氧相亲关系,对Mycobacterium tuberculosis中缺氧适应有意义

Elizabeth A Apiche¹, Eaindra Yee¹, Anoop Rama Damodaran¹

¹Department of Chemistry, University of Minnesota, Minneapolis, MN 5545, United States of America.

Journal of inorganic biochemistry

|May 18, 2024

概括

在Mycobacterium tuberculosis中基于血红蛋白的激酶DosT和DosS感知氧气水平. 它们的修订后,更强的氧结合亲和力揭示了结核病休眠期和耐药性的新见解.

科学领域:

生物化学生物化学
微生物学微生物学
分子生物学分子生物学

背景情况:

DosT和DosS是基于血红素的激酶,对于在Mycobacterium tuberculosis (Mtb) 中感知氧气 (O2) 至关重要.
这些蛋白质在低氧气条件下调节>50个休眠基因,影响结核病 (TB) 感染,休眠和耐药性.

研究的目的:

重新检查并准确量化DosT和DosS的O2结合亲缘关系.
为了将这些结合特性与Mtb对缺氧的反应相关联.

主要方法:

确定了DosT和DosS O2 结合的平衡分离常数 (Kd).
停止流动动力学被用来测量协会 (kon) 和解离 (koff) 速率常数.

主要成果:

DosT和DosS的O2结合比以前报告的要强得多 (Kd值分别为3.3±1.0μM和0.46±0.08μM).
动力学研究显示,对于这两种激酶来说,O2结合和解离的速度常数是不同的.
这些更紧密的结合常数与韦恩模型中低氧诱导的非复制性持久性的特定阶段相关.

结论:

对DosT和DosS的修订后的O2结合参数提供了对它们在Mtb中的功能更准确的了解.
这种增强的知识有助于进一步研究MTB中缺氧适应和信号传导的机制.
这些发现可能会为针对结核病休眠期和耐药性的策略提供信息.

关键词:

黑米铁是什么黑米铁是什么氧气过低是因为缺氧.微生物微生物氧气传感器氧气传感器氧化还原信号传递.结核病是一种疾病.

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