AI Article Synopsis
- The Zika virus NS2B-NS3 protease is targeted for drug development, and its usual structural study construct features a glycine-rich linker between NS2B and NS3.
- Using NMR spectroscopy, researchers analyzed the conventional Zika protease (gZiPro), finding that while the linker doesn't change the protein's overall folding, it causes heterogeneity during ion exchange chromatography.
- The study highlights differences in the chemical environment of several residues, including H51 in the catalytic triad, between linked and unlinked Zika protease constructs.
Article Abstract
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.
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| http://dx.doi.org/10.1002/1873-3468.12741 | DOI Listing |
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