6VG5
DengueV-2 Capsid ST148 inhibitor Complex
Summary for 6VG5
| Entry DOI | 10.2210/pdb6vg5/pdb |
| Descriptor | Capsid premembrane protein, NITRATE ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | dengue, capsid, inhibitor, viral protein, viral protein-inhibitor complex, viral protein/inhibitor |
| Biological source | Dengue virus 2 |
| Total number of polymer chains | 2 |
| Total formula weight | 20274.81 |
| Authors | |
| Primary citation | Xia, H.,Xie, X.,Zou, J.,Noble, C.G.,Russell, W.K.,Holthauzen, L.M.F.,Choi, K.H.,White, M.A.,Shi, P.Y. A cocrystal structure of dengue capsid protein in complex of inhibitor. Proc.Natl.Acad.Sci.USA, 117:17992-18001, 2020 Cited by PubMed Abstract: Dengue virus (DENV) was designated as a top 10 public health threat by the World Health Organization in 2019. No clinically approved anti-DENV drug is currently available. Here we report the high-resolution cocrystal structure (1.5 Å) of the DENV-2 capsid protein in complex with an inhibitor that potently suppresses DENV-2 but not other DENV serotypes. The inhibitor induces a "kissing" interaction between two capsid dimers. The inhibitor-bound capsid tetramers are assembled inside virions, resulting in defective uncoating of nucleocapsid when infecting new cells. Resistant DENV-2 emerges through one mutation that abolishes hydrogen bonds in the capsid structure, leading to a loss of compound binding. Structure-based analysis has defined the amino acids responsible for the inhibitor's inefficacy against other DENV serotypes. The results have uncovered an antiviral mechanism through inhibitor-induced tetramerization of the viral capsid and provided essential structural and functional knowledge for rational design of panserotype DENV capsid inhibitors. PubMed: 32669438DOI: 10.1073/pnas.2003056117 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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