Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion

被引：247

作者：

Russell, Rupert J. ^{[1
]}

Kerry, Philip S. ^{[1
]}

Stevens, David J. ^{[2
]}

Steinhauer, David A. ^{[3
]}

Martin, Stephen R. ^{[2
]}

Gamblin, Steven J. ^{[2
]}

Skehel, John J. ^{[2
]}

机构：

[1] Univ St Andrews, Sch Biol, Interdisciplinary Ctr Human & Avian Influenza Res, St Andrews KY16 9ST, Fife, Scotland

[2] Natl Inst Med Res, MRC, Mill Hill NW7 1AA, England

[3] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 46期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

crystallography; drug design;

D O I：

10.1073/pnas.0807142105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The influenza surface glycoprotein hemagglutinin (HA) is a potential target for antiviral drugs because of its key roles in the initial stages of infection: receptor binding and the fusion of virus and cell membranes. The structure of HA in complex with a known inhibitor of membrane fusion and virus infectivity, tert-butyl hydroquinone (TBHQ), shows that the inhibitor binds in a hydrophobic pocket formed at an interface between HA monomers. Occupation of this site by TBHQ stabilizes the neutral pH structure through intersubunit and intrasubunit interactions that presumably inhibit the conformational rearrangements required for membrane fusion. The nature of the binding site suggests routes for the chemical modification of TBHQ that could lead to the development of more potent inhibitors of membrane fusion and potential anti-influenza drugs.

引用

页码：17736 / 17741

页数：6

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