6BR5

N2 neuraminidase in complex with a novel antiviral compound

6BR5 の概要

• エントリーDOI: 10.2210/pdb6br5/pdb
• 分子名称: Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: complex, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Influenza A virus (A/Perth/16/2009(H3N2))
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45014.94

構造登録者

Li, L.H.,Ve, T.,Pascolutti, M.,Hadhazi, A.,Bailly, B.,Thomson, R.J.,Gao, G.F.,von Itzstein, M. (登録日: 2017-11-30, 公開日: 2018-03-07, 最終更新日: 2024-10-23)

主引用文献

Hadhazi, A.,Li, L.,Bailly, B.,Maggioni, A.,Martin, G.,Dirr, L.,Dyason, J.C.,Thomson, R.J.,Gao, G.F.,Borbas, A.,Ve, T.,Pascolutti, M.,von Itzstein, M.
A Sulfonozanamivir Analogue Has Potent Anti-influenza Virus Activity.
ChemMedChem, 13:785-789, 2018

PubMed Abstract: Influenza virus infection continues to cause significant, often severe, respiratory illness worldwide. A validated target for the development of anti-influenza agents is the virus surface protein sialidase. In the current study, we have discovered a highly potent inhibitor of influenza virus sialidase, based on a novel sialosyl sulfonate template. The synthesised 3-guanidino sialosyl α-sulfonate, a sulfonozanamivir analogue, inhibits viral replication in vitro at the nanomolar level, comparable to that of the anti-influenza drug zanamivir. Using protein X-ray crystallography we show that the sialosyl α-sulfonate template binds within the sialidase active site in a C chair conformation. The C1-sulfonate moiety forms crucial and strong-binding interactions with the active site's triarginyl cluster, while the 3-guanidino moiety interacts significantly with conserved active site residues. This sulfonozanamivir analogue provides a new direction in anti-influenza virus drug development.

PubMed: 29453852
DOI: 10.1002/cmdc.201800092

実験手法

X-RAY DIFFRACTION (2.03790748321 Å)