CCR5化学因子受体-HIV入口抑制剂马拉维罗克复合物的结构
Qiuxiang Tan1, Ya Zhu, Jian Li
1CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai, China 201203.
概括
与马拉维罗克结合的CCR5共受体的晶体结构揭示了一个新的药物结合部位. 这一发现为开发HIV-1治疗方法提供了新的策略,通过准病毒进入.
科学领域:
- 结构生物学 结构生物学
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
背景情况:
- CCR5化学受体对于HIV-1进入宿主细胞至关重要.
- 了解CCR5结构是设计有效的HIV-1抑制剂的关键.
研究的目的:
- 为了确定与maraviroc.结合的人类CCR5的高分辨率晶体结构.
- 阐明马拉维洛克对CCR5.5的全抑制机制.
- 调查HIV-1共受体选择性的决定因素.
主要方法:
- 在2.7安格斯特罗姆分辨率的X射线晶体学.
- CCR5和CXCR4的结构比较.
- 同受体-gp120-V3复合物的建模.
主要成果:
- 确定了与马拉维罗克结合的人类CCR5的晶体结构.
- 鉴定了马拉维洛克的一个独特的结合位,与化学和gp120结合位分开.
- CCR5和CXCR4之间的结构差异表明HIV-1共受体选择性的机制.
结论:
- CCR5-maraviroc结构提供了对病毒进入的全抑制的见解.
- 基于结构的药物设计可以用于新的HIV-1治疗方法.
- 了解共同受体选择性对于对抗HIV-1感染至关重要.
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