Structural highlights
Function
[H8XX12_ZIKV] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[SAAS:SAAS00882589]
Publication Abstract from PubMed
The NS2B-NS3 viral protease is an attractive drug target against Zika virus (ZIKV) due to its importance in viral replication and maturation. Here we report the crystal structure of protease in complex with a dipeptide inhibitor, Acyl-KR-aldehyde (compound 1). The aldehyde moiety forms a covalent bond with the catalytic Ser(135) of NS3. The Arg and Lys residues in the inhibitor occupy the S1 and S2 sites of the protease, respectively. Nuclear magnetic resonance studies demonstrate that the complex is in the closed conformation in solution. The chemical environment of residues surrounding the active site is sensitive to the bound inhibitor as demonstrated by the comparison with two other non-covalent dipeptides, Acyl-K-Agmatine (compound 2) and Acyl-KR-COOH (compound 3). Removing the aldehyde moiety in 1 converts the binding mode from a slow to a fast exchange regime. The structural dynamics information obtained in this study will guide future drug discovery against ZIKV and other flaviviruses.
Structural Dynamics of Zika Virus NS2B-NS3 Protease Binding to Dipeptide Inhibitors.,Li Y, Zhang Z, Phoo WW, Loh YR, Wang W, Liu S, Chen MW, Hung AW, Keller TH, Luo D, Kang C Structure. 2017 Aug 1;25(8):1242-1250.e3. doi: 10.1016/j.str.2017.06.006. Epub, 2017 Jul 6. PMID:28689970[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li Y, Zhang Z, Phoo WW, Loh YR, Wang W, Liu S, Chen MW, Hung AW, Keller TH, Luo D, Kang C. Structural Dynamics of Zika Virus NS2B-NS3 Protease Binding to Dipeptide Inhibitors. Structure. 2017 Aug 1;25(8):1242-1250.e3. doi: 10.1016/j.str.2017.06.006. Epub, 2017 Jul 6. PMID:28689970 doi:http://dx.doi.org/10.1016/j.str.2017.06.006
