5gj4

From Proteopedia

Structure of NS2B-NS3 Protease from Zika Virus caught after self-cleavage

Structural highlights

5gj4 is a 8 chain structure with sequence from Zika virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.839Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

POLG_ZIKV Protein C: Encapsulates the genomic RNA.[UniProtKB:P17763] prM: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated.[UniProtKB:P17763] Envelope protein E: Binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes.[UniProtKB:P17763] Non-structural protein 1: Involved in virus replication and regulation of the innate immune response.[UniProtKB:P17763] Non-structural protein 2A: May be involved viral RNA replication and capsid assembly.[UniProtKB:P09732] Non-structural protein 4A: Induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the helicase region of Serine protease NS3 chain.[UniProtKB:P17763] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[UniProtKB:P17763] Non-structural protein 4B: Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway.[UniProtKB:P17763]

Publication Abstract from PubMed

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 A 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.

Structure of the NS2B-NS3 protease from Zika virus after self-cleavage.,Phoo WW, Li Y, Zhang Z, Lee MY, Loh YR, Tan YB, Ng EY, Lescar J, Kang C, Luo D Nat Commun. 2016 Nov 15;7:13410. doi: 10.1038/ncomms13410. PMID:27845325^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Phoo WW, Li Y, Zhang Z, Lee MY, Loh YR, Tan YB, Ng EY, Lescar J, Kang C, Luo D. Structure of the NS2B-NS3 protease from Zika virus after self-cleavage. Nat Commun. 2016 Nov 15;7:13410. doi: 10.1038/ncomms13410. PMID:27845325 doi:http://dx.doi.org/10.1038/ncomms13410