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Crystal structure of unlinked NS2B-NS3 protease from Zika virus

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Science  08 Dec 2016:
aai9309
DOI: 10.1126/science.aai9309

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Abstract

Zika virus (ZIKV) has rapidly emerged as a global public health concern. Viral NS2B-NS3 protease processes viral polyprotein and is essential for the virus replication, making it an attractive antiviral drug target. We report crystal structures of the unlinked NS2B-NS3 protease from ZIKV as free enzyme and bound to a peptide reversely oriented at the active site at 1.58 Å resolution. The unlinked NS2B-NS3 protease adopts a closed conformation in which NS2B engages NS3 to form an empty substrate binding site. A second protease in the same crystal binds to the residues K14K15G16E17 from the neighboring NS3 in reverse orientation resisting proteolysis. These features of ZIKV NS2B-NS3 protease may accelerate structure-based antiviral drug discovery against ZIKV and related pathogenic flaviviruses.

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