Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus

Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus
Title:
Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus
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Science
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Publication Date:
23 December 2016
Citation:
Science 23 Dec 2016: Vol. 354, Issue 6319, pp. 1597-1600
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.
License type:
PublisherCopyrights
Funding Info:
Lee Kong Chian School of Medicine, Nanyang Technological University, National Medical Research Council grant CBRG15May045, A*STAR JCO grant (1431AFG102/1331A028)
Description:
ISSN:
0036-8075
1095-9203
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