Format

Send to

Choose Destination
Science. 2016 Dec 23;354(6319):1597-1600. doi: 10.1126/science.aai9309. Epub 2016 Dec 8.

Crystal structure of unlinked NS2B-NS3 protease from Zika virus.

Zhang Z1,2, Li Y3, Loh YR3, Phoo WW1,2,4, Hung AW3, Kang C5, Luo D6,2.

Author information

1
Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building 03-07, 59 Nanyang Drive, Singapore 636921.
2
NTU Institute of Structural Biology, Nanyang Technological University, Experimental Medicine Building 06-01, 59 Nanyang Drive, Singapore 636921.
3
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669.
4
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
5
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669. cbkang@etc.a-star.edu.sg luodahai@ntu.edu.sg.
6
Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building 03-07, 59 Nanyang Drive, Singapore 636921. cbkang@etc.a-star.edu.sg luodahai@ntu.edu.sg.

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 at 1.58-angstrom resolution of the unlinked NS2B-NS3 protease from ZIKV as free enzyme and bound to a peptide reversely oriented at the active site. 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 the discovery of structure-based antiviral drugs against ZIKV and related pathogenic flaviviruses.

PMID:
27940580
DOI:
10.1126/science.aai9309
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center