Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1.
Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1.
复制标题
结核分枝杆菌伸长因子 G1 的晶体结构
DOI：
10.3389/fmolb.2021.667638
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发表时间：
2021
影响因子：
5
通讯作者：
Cui S
中科院分区：
文献类型：
--
作者：
Gao X;Yu X;Zhu K;Qin B;Wang W;Han P;Aleksandra Wojdyla J;Wang M;Cui S
2019 年，结核分枝杆菌 (Mtb) 估计在全球造成 1000 万例结核病例和 120 万人死亡。多重耐药和广泛耐药 Mtb 的不断出现正在成为全球公共卫生威胁，使得抗 Mtb 药物靶点的识别变得刻不容缓。延伸因子 G (EF-G) 参与蛋白质翻译过程中核糖体上的 tRNA 易位。因此，EF-G是结构分析的一个重点，也是抗生素的一个有价值的药物靶点。然而，Mtb EF-G1的晶体结构尚不清楚，这限制了抑制剂的设计。在这里，我们报告了 Mtb EF-G1 与 GDP 复合物的晶体结构。 Mtb EF-G1-GDP 复合物的独特晶体形式为使用晶体学方法进行基于片段的筛选提供了一个极好的平台。我们的研究结果为 GDP 识别提供了基于结构的解释，并有助于识别在药物发现背景下具有潜在兴趣的 EF-G1 抑制剂。
Mycobacterium tuberculosis (Mtb) caused an estimated 10 million cases of tuberculosis and 1.2 million deaths in 2019 globally. The increasing emergence of multidrug-resistant and extensively drug-resistant Mtb is becoming a public health threat worldwide and makes the identification of anti-Mtb drug targets urgent. Elongation factor G (EF-G) is involved in tRNA translocation on ribosomes during protein translation. Therefore, EF-G is a major focus of structural analysis and a valuable drug target of antibiotics. However, the crystal structure of Mtb EF-G1 is not yet available, and this has limited the design of inhibitors. Here, we report the crystal structure of Mtb EF-G1 in complex with GDP. The unique crystal form of the Mtb EF-G1-GDP complex provides an excellent platform for fragment-based screening using a crystallographic approach. Our findings provide a structure-based explanation for GDP recognition, and facilitate the identification of EF-G1 inhibitors with potential interest in the context of drug discovery.