X-ray structures of NS1 effector domain mutants

被引：21

作者：

Xia, Shuangluo ^{[1
]}

Robertus, Jon D. ^{[1
]}

机构：

[1] Univ Texas Austin, Dept Chem & Biochem, Inst Mol & Cellular Biol, Austin, TX 78712 USA

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2010年 / 494卷 / 02期

关键词：

NS1 effector domain; Influenza protein; Drug target; Protein engineering; INFLUENZA-A VIRUS; PRE-MESSENGER-RNAS; PROTEIN; BINDING; CLEAVAGE; SUBUNIT; SITE; CPSF;

D O I：

10.1016/j.abb.2009.12.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The influenza A virus nonstructural protein NS1 is a multifunctional dimeric protein that acts as a potent inhibitor of the host cellular antiviral state. The C-terminal effector domain of NS1 binds host proteins, including CPSF30, and is a target for the development of new antiviral drugs. Here we present crystallographic structures of two mutant effector domains, W187Y and W187A, of influenza A/Udorn/72 virus. Unlike wild-type, the mutants behave exclusively as monomers in solution based on gel filtration data and light scattering. The W187Y mutant is able to bind CPSF30 with a binding affinity close to the wild-type protein; that is, it retains a receptor site for aromatic ligands nearly identical to the wild-type. Therefore, this monomeric mutant protein could serve as a drug target for a high throughput inhibitor screening assays, since its binding pocket is unoccupied in solution and potentially more accessible to small molecule ligands. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：198 / 204

页数：7

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