DapB是解决Mycobacterium tuberculosis的抗菌素耐药性的一个保存目标
Pratik Mahajan1,2, Hetarth Gor1, Manali Joshi2
1ICMR - National Institute of Translational Virology and AIDS Research (formerly NARI), Pune, India.
Journal of biomolecular structure & dynamics
|November 6, 2025
概括
结核病耐药性需要新的目标. 这项研究表明,DapB酶在Mycobacterium tuberculosis中被保存,这表明它有可能成为结核病治疗的药物标.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
背景情况:
- 结核病 (TB) 是一个全球性的健康挑战,因药物耐药性而加剧,需要新的治疗目标.
- 结核菌菌 (Mtb) dapB基因编码了二二烯酸酸缩酶 (DapB),对于氨酸生物合成至关重要,这种途径在人类中不存在,使其成为一个有前途的目标.
研究的目的:
- 为了研究Mtb dapB基因及其编码的DapB酶的保存.
- 从临床隔离物和公共数据库中识别和描述dappB的突变.
- 通过原子模拟来评估已识别的突变对DapB蛋白结构和功能的影响.
主要方法:
- 从72个印度Mtb临床分离物中对DapB基因进行DNA放大和测序.
- 在BV-BRC数据库中对310万亿倍的分离物 dapB基因组数据进行生物信息分析.
- 在野生类型和突变DapB蛋白质的in silico原子模拟中评估结构和功能完整性.
主要成果:
- 序列分析揭示了临床分离物中的一个非同名突变 (DapB_65) 和一个 (DapB_89) 在BV-BRC分离物中,以及两个同名突变.
- 鉴定的突变位于蛋白质表面,距离活性部位远 (> 1.0 nm).
- 原子模拟显示,原生DapB和突变DapB之间的整体蛋白质结构或活性位体尺寸没有显著的变化.
结论:
- 该DapB酶在Mtb分离物中表现出高保护性,表明其作为可行的药物点的潜力.
- 鉴定到的突变似乎不会对DapB的结构或功能产生重大影响,从而加强了其适用于治疗干预的适用性.
- 在开发新的抗结核药物以对抗耐药菌株方面,DapB是一个有前途的目标.
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