Structural characterization of the linked NS2B-NS3 protease of Zika virus.
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.
['Li|Yan|Y|', 'Phoo|Wint Wint|WW|', 'Loh|Ying Ru|YR|', 'Zhang|Zhenzhen|Z|', 'Ng|Elizabeth Yihui|EY|', 'Wang|Weiling|W|', 'Keller|Thomas H|TH|', 'Luo|Dahai|D|', 'Kang|CongBao|C|']
D020134:Catalytic Domain D002852:Chromatography, Ion Exchange D019906:Nuclear Magnetic Resonance, Biomolecular D011487:Protein Conformation D017510:Protein Folding D011994:Recombinant Proteins D012697:Serine Endopeptidases D015842:Serine Proteinase Inhibitors D014764:Viral Proteins D000071244:Zika Virus
structure protease Zika virus NMR drug discovery protein dynamics