Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5

doi:10.1038/s41401-018-0054-2

	Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5
	Zhu, Ya 1,2; Zhao, Yan-long1,2,3 ; Li, Jian 1,4; Liu, Hong 1,4; Zhao, Qiang 1,2,4,5; Wu, Bei-li1,2,3,5 ; Yang, Zhen-lin 1,4
	2019-04
发表期刊	ACTA PHARMACOLOGICA SINICA
ISSN	1671-4083
卷号	40 期号:4 页码:563-568
发表状态	已发表
DOI	10.1038/s41401-018-0054-2
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 A 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.
关键词	CCR5 anti-HIV PF-232798 maraviroc antagonist crystal structure
收录类别	SCI ; SCIE ; CSCD
语种	英语
资助项目	National Natural Science Foundation of China[31730027]
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
WOS类目	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号	WOS:000462854600017
出版者	ACTA PHARMACOLOGICA SINICA
WOS关键词	ALLOSTERIC MODULATION ; INHIBITOR ; ENTRY ; REFINEMENT
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34185
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_吴蓓丽组
通讯作者	Wu, Bei-li; Yang, Zhen-lin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Ctr Excellence Biomacromol, Beijing 100101, Peoples R China
通讯作者单位	生命科学与技术学院
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,2019,40(4):563-568.
APA	Zhu, Ya.,Zhao, Yan-long.,Li, Jian.,Liu, Hong.,Zhao, Qiang.,...&Yang, Zhen-lin.(2019).Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5.ACTA PHARMACOLOGICA SINICA,40(4),563-568.
MLA	Zhu, Ya,et al."Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5".ACTA PHARMACOLOGICA SINICA 40.4(2019):563-568.