Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5
文献类型：期刊论文
| 作者 | Zhu, Ya; Zhao, Yan-Long; Li, Jian; Liu, Hong ; Zhao, Qiang; Wu, Bei-Li; Yang, Zhen-Lin
|
| 刊名 | Acta pharmacologica Sinica
 |
| 出版日期 | 2018-06-25 |
| ISSN号 | 1745-7254 |
| DOI | 10.1038/s41401-018-0054-2 |
| 文献子类 | Article |
| 英文摘要 | The chemokine receptor CCR5 is an important anti-HIV (human immunodeficiency virus) drug target owning to its pivotal role in HIV-1 viral entry as a co-receptor. Here, we present a 2.9 Å resolution crystal structure of CCR5 bound to PF-232798, a second-generation oral CCR5 antagonist currently in phase II clinical trials. PF-232798 and the marketed HIV drug maraviroc share a similar tropane scaffold with different amino (N)- and carboxyl (C)- substituents. Comparison of the CCR5-PF-232798 structure with the previously determined structure of CCR5 in complex with maraviroc reveals different binding modes of the two allosteric antagonists and subsequent conformational changes of the receptor. Our results not only offer insights into the phenomenon that PF-232798 has higher affinity and alternative resistance profile to maraviroc, but also will facilitate the design of new anti-HIV drugs. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266779]  |
| 专题 | 新药研究国家重点实验室 药物靶标结构与功能中心 |
| 通讯作者 | Wu, Bei-Li; Yang, Zhen-Lin |
| 作者单位 | Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China |
| 推荐引用方式 GB/T 7714 | Zhu, Ya,Zhao, Yan-Long,Li, Jian,et al. Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5[J]. Acta pharmacologica Sinica,2018. |
| APA | Zhu, Ya.,Zhao, Yan-Long.,Li, Jian.,Liu, Hong.,Zhao, Qiang.,...&Yang, Zhen-Lin.(2018).Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5.Acta pharmacologica Sinica. |
| MLA | Zhu, Ya,et al."Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5".Acta pharmacologica Sinica (2018). |
入库方式： OAI收割
来源：上海药物研究所
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