Structural characterization of the linked NS2B-NS3 protease of Zika virus

被引：32

作者：

Li, Yan ^{[1
]}

Phoo, Wint Wint ^{[2
,3
,4
]}

Loh, Ying Ru ^{[1
]}

Zhang, Zhenzhen ^{[2
,3
]}

Ng, Elizabeth Yihui ^{[1
]}

Wang, Weiling ^{[1
]}

Keller, Thomas H. ^{[1
]}

Luo, Dahai ^{[2
,3
]}

Kang, CongBao ^{[1
]}

机构：

[1] ASTAR, Expt Therapeut Ctr, 31 Biopolis Way,Nanos 03-01, Singapore 138669, Singapore

[2] Nanyang Technol Univ, Lee Kong Chian Sch Med, EMB 03-07,59 Nanyang Dr, Singapore 636921, Singapore

[3] Nanyang Technol Univ, NTU Inst Struct Biol, Singapore, Singapore

[4] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore

来源：

FEBS LETTERS | 2017年 / 591卷 / 15期

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

drug discovery; NMR; protease; protein dynamics; structure; Zika virus; WEST-NILE-VIRUS; DENGUE VIRUS; NS3; PROTEASE; CRYSTAL-STRUCTURE; INHIBITORS; HELICASE; BINDING; NMR; CONFORMATION; ACTIVATION;

D O I：

10.1002/1873-3468.12741

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 Zika virus (ZIKV) NS2B-NS3 protease is an important drug target. The conventional flaviviral protease constructs used for structural studies contain the NS2B cofactor region linked to the NS3 protease domain via a glycine-rich flexible linker. Here, we examined the structural dynamics of this conventional Zika protease (gZiPro) using NMR spectroscopy. Although the glycine-rich linker in gZiPro does not alter the overall folding of the protease in solution, gZiPro is not homogenous in ion exchange chromatography. Compared to the unlinked protease construct, the artificial linker affects the chemical environment of many residues including H51 in the catalytic triad. Our study provides a direct comparison of ZIKV protease constructs with and without an artificial linker.

引用

页码：2338 / 2347

页数：10

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