7VXY

Zika virus NS2B/NS3 protease bZipro(C143S) in complex with D-RKOR

7VXY の概要

• エントリーDOI: 10.2210/pdb7vxy/pdb
• 分子名称: Serine protease subunit NS2B, Serine protease NS3, Peptide inhibitor, ... (4 entities in total)
• 機能のキーワード: zikv, ns2b/ns3 protease, inhibitor, complex, viral protein
• 由来する生物種: Zika virus; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 52155.61

構造登録者

Xiong, Y.C.,Cheng, F.,Zhang, J.Y.,Su, H.X.,Hu, H.C.,Zou, Y.,Li, M.J.,Xu, Y.C. (登録日: 2021-11-13, 公開日: 2022-09-14, 最終更新日: 2023-11-29)

主引用文献

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

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: 36049322
DOI: 10.1016/j.bioorg.2022.106109

実験手法

X-RAY DIFFRACTION (1.901 Å)