7VXX
Zika virus NS2B/NS3 protease bZipro(C143S) in complex with 4-amino benzamidine
Summary for 7VXX
| Entry DOI | 10.2210/pdb7vxx/pdb |
| Descriptor | Serine protease subunit NS2B, Serine protease NS3, P-AMINO BENZAMIDINE, ... (4 entities in total) |
| Functional Keywords | zikv, ns2b/ns3 protease, inhibitor, complex, viral protein |
| Biological source | Zika virus More |
| Total number of polymer chains | 4 |
| Total formula weight | 51716.06 |
| Authors | Xiong, Y.C.,Cheng, F.,Zhang, J.Y.,Su, H.X.,Hu, H.C.,Zou, Y.,Li, M.J.,Xu, Y.C. (deposition date: 2021-11-13, release date: 2022-09-14, Last modification date: 2023-11-29) |
| Primary citation | Xiong, Y.,Cheng, F.,Zhang, J.,Su, H.,Hu, H.,Zou, Y.,Li, M.,Xu, Y. Structure-based design of a novel inhibitor of the ZIKA virus NS2B/NS3 protease. Bioorg.Chem., 128:106109-106109, 2022 Cited by PubMed Abstract: Zika virus (ZIKV) has been a serious public health problem, and there is no vaccine or drug approved for the prevention or treatment of ZIKV yet. The ZIKV NS2B/NS3 protease plays an important role in processing the virus precursor polyprotein and is thus a promising target for antiviral drugs development. In order to discover novel inhibitors of this protease, we carried out a fragment-based hit screening and characterized protein-inhibitor interactions using the X-ray crystallography together with isothermal titration calorimetry. We reported two high-resolution crystal structures of the protease (bZiPro) in complex with an active fragment as well as a tetrapeptide, revealing that there is domain swapping in the protein structures and two ligands only occupy the substrate-binding pocket of one copy in a symmetric unit. Based on the detailed binding modes of two ligands revealed by crystal structures, we designed a novel inhibitor which inhibits the NS2B/NS3 protease with a higher potency than the fragment and possesses a higher ligand-binding efficiency and a comparable IC compared to the tetrapeptide. These results thus provide a structural basis and valuable hint for development of more potent inhibitors of the ZIKV NS2B/NS3 protease. PubMed: 36049322DOI: 10.1016/j.bioorg.2022.106109 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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