Structural highlights
Function
A0A140DLX4_ZIKV Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504] Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3.[PROSITE-ProRule:PRU00859]
Publication Abstract from PubMed
The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 A crystal structure of ZIKV protease in complex with a peptidomimetic boronic-acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the non-conserved Asp83 of NS2B, Ion-pairing between Asp83 and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing.
Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor.,Lei J, Hansen G, Nitsche C, Klein CD, Zhang L, Hilgenfeld R Science. 2016 Jul 7. pii: aag2419. PMID:27386922[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lei J, Hansen G, Nitsche C, Klein CD, Zhang L, Hilgenfeld R. Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor. Science. 2016 Jul 7. pii: aag2419. PMID:27386922 doi:http://dx.doi.org/10.1126/science.aag2419
