气候变化领域集成服务门户(CCPortal): Structural basis for strand-transfer inhibitor binding to HIV intasomes

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DOI	10.1126/science.aay8015
	Structural basis for strand-transfer inhibitor binding to HIV intasomes
	Passos D.O.; Li M.; Jóźwik I.K.; Zhao X.Z.; Santos-Martins D.; Yang R.; Smith S.J.; Jeon Y.; Forli S.; Hughes S.H.; Burke T.R.; Jr.; Craigie R.; Lyumkis D.
发表日期	2020
ISSN	0036-8075
起始页码	810
结束页码	814
卷号	367 期号:6479
英文摘要	The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretroviral drugs, integrase strand-transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy structures of HIV intasomes bound to the latest generation of INSTIs. These structures highlight how small changes in the integrase active site can have notable implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug-resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	bictegravir nucleoprotein protein intasome unclassified drug viral protein bictegravir fused heterocyclic rings integrase integrase inhibitor multiprotein complex naphthyridine derivative nucleoprotein biochemistry chemical binding human immunodeficiency virus inhibitor protein ultrastructure amino terminal sequence Article carboxy terminal sequence catalysis cryoelectron microscopy drug design drug efficacy drug protein binding drug resistance drug structure enzyme active site human Human immunodeficiency virus infection nonhuman priority journal protein purification protein structure antiviral resistance chemistry drug effect genetics Human immunodeficiency virus virus DNA cell DNA interaction Cryoelectron Microscopy Drug Design Drug Resistance, Viral Heterocyclic Compounds, 4 or More Rings HIV HIV Integrase HIV Integrase Inhibitors Humans Multiprotein Complexes Naphthyridines Nucleoproteins Virus Integration
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133706
推荐引用方式 GB/T 7714	Passos D.O.,Li M.,Jóźwik I.K.,et al. Structural basis for strand-transfer inhibitor binding to HIV intasomes[J]. Science,2020,367(6479).
APA	Passos D.O..,Li M..,Jóźwik I.K..,Zhao X.Z..,Santos-Martins D..,...&Lyumkis D..(2020).Structural basis for strand-transfer inhibitor binding to HIV intasomes.,367(6479).
MLA	Passos D.O.,et al."Structural basis for strand-transfer inhibitor binding to HIV intasomes".367.6479(2020).