7ZNO

Crystal Structure of Unlinked NS2B_NS3 Protease from Zika Virus in Complex with Boronate Inhibitor MI-2270

7ZNO の概要

• エントリーDOI: 10.2210/pdb7zno/pdb
• 分子名称: Serine protease subunit NS2B, Serine protease NS3, [(1R)-1-[[(2S)-6-azanyl-2-[[(2S)-6-azanyl-2-[2-[3-(4-carbamimidamido-3-oxidanylidene-pentyl)phenyl]ethanoylamino]hexanoyl]amino]hexanoyl]amino]-3-methyl-butyl]boronic acid, ... (4 entities in total)
• 機能のキーワード: flavivirin, serine protease, viral protein, ns2b-ns3, zika virus, boronic acid, boronate
• 由来する生物種: Zika virus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25549.61

構造登録者

Huber, S.,Heine, A.,Steinmetzer, T. (登録日: 2022-04-21, 公開日: 2022-06-22, 最終更新日: 2024-02-07)

主引用文献

Braun, N.J.,Huber, S.,Schmacke, L.C.,Heine, A.,Steinmetzer, T.
Boroleucine-Derived Covalent Inhibitors of the ZIKV Protease.
Chemmedchem, 18:e202200336-e202200336, 2023

PubMed Abstract: The Zika virus (ZIKV) remains a potential threat to the public health due to the lack of both an approved vaccination or a specific treatment. In this work, a series of peptidic inhibitors of the ZIKV protease with boroleucine as P1 residue was synthesized. The highest affinities with K values down to 8 nM were observed for compounds with basic residues in both P2 and P3 position and at the N-terminus. The low potency of reference compounds containing leucine, leucine-amide or isopentylamide as P1 residue suggested a covalent binding mode of the boroleucine-derived inhibitors. This was finally proven by crystal structure determination of the most potent inhibitor from this series in complex with the ZIKV protease.

PubMed: 36325810
DOI: 10.1002/cmdc.202200336

実験手法

X-RAY DIFFRACTION (1.7 Å)