Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Nat Commun. 2016 Nov 15;7:13410. doi: 10.1038/ncomms13410.

Structure of the NS2B-NS3 protease from Zika virus after self-cleavage.

Phoo WW1,2,3, Li Y4, Zhang Z1,3, Lee MY4, Loh YR4, Tan YB1,3, Ng EY4, Lescar J2,3, Kang C4, Luo D1,2,3.

Author information

1
Lee Kong Chian School of Medicine, Nanyang Technological University, EMB 03-07, 59 Nanyang Drive, Singapore 636921, Singapore.
2
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 636921, Singapore.
3
NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, Singapore 636921, Singapore.
4
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis way, Nanos, #03-01, Singapore 138669, Singapore.

Abstract

The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.84 Å resolution of ZIKV non-structural protein NS2B-NS3 protease with the last four amino acids of the NS2B cofactor bound at the NS3 active site. This structure represents a post-proteolysis state of the enzyme during viral polyprotein processing and provides insights into peptide substrate recognition by the protease. Nuclear magnetic resonance (NMR) studies and protease activity assays unravel the protein dynamics upon binding the protease inhibitor BPTI in solution and confirm this finding. The structural and functional insights of the ZIKV protease presented here should advance our current understanding of flavivirus replication and accelerate structure-based antiviral drug discovery against ZIKV.

PMID:
27845325
PMCID:
PMC5116066
DOI:
10.1038/ncomms13410
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center