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挖掘 B-人 STING 相互作用的计算分析暗示了一个Cys148-相邻的走廊,具有洞内子位的多样性

Tien-Lin Chang¹, Hsiao-Yu Sun², Ping-Jyun Sung^3,4

¹Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan.

International journal of molecular sciences

|March 14, 2026

概括

挖掘B (ExcB) 通过结合一个神秘的口袋来非共价调节STING通路,为炎症驱动的癌症,如结直肠癌 (CRC) 提供了一种新的治疗策略. 这项研究为开发新型STING调制器提供了结构基础.

科学领域:

分子生物学分子生物学
结构生物学是结构生物学.
计算化学是一种计算化学.

背景情况:

慢性炎症,特别是结肠炎相关的结肠直肠癌 (CRC),是由失调的免疫信号驱动的.
cGAS-STING通路是先天免疫的中心调节者,但由于其在不足和过度活动中的复杂作用,它带来了治疗挑战.
准STING通路为治疗炎症性疾病和癌症提供了潜在的潜力.

研究的目的:

为了结构性地描述海洋二类物体excavatolide B (ExcB) 与人类STING (hSTING) 循环二核酸 (CDN) 结合裂的相互作用.
阐明ExcB调节hSTING活动的机制.
为开发针对STING的新型治疗方法建立结构性基础.

主要方法:

集成AlphaFold3 (AF3) 用于hSTING建模.
基于扩散的对接和明确溶剂分子动力学 (MD) 模拟来分析ExcB结合.
对AF3模型与实验结构 (PDB: 4EF5, 6A05) 的验证以及对残留物相互作用和构造变化的分析.

主要成果:

ExcB通过主要非共价相互作用与hSTING CDN结合裂内的非正规位点 (位点-2') 结合.
结合机制涉及受体重塑 (符合条件),而不是直接与原生激动剂cGAMP发生硬质冲突.
ExcB结合导致cGAMP的对接结果不那么有利,这表明抑制调节.

结论:

挖掘剂B作为hSTING的非共价调制器,准CDN结合裂内的神秘口袋.
这些发现提供了对ExcB-hSTING相互作用的详细结构理解.
这项研究为结构-活性关系 (SAR) 研究和向突变发生的研究奠定了基础,以开发新的STING通路调节器.

关键词:

接收人接收人刺痛是一种刺痛.布里亚纳尼 (Briarane) 是一种二氧化的二氧化物.结肠炎相关的结肠直肠癌计算对接的计算对接分子动力学分子动力学

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