1L7F

Crystal structure of influenza virus neuraminidase in complex with BCX-1812

1L7F の概要

• エントリーDOI: 10.2210/pdb1l7f/pdb
• 関連するPDBエントリー: 1L7G 1L7H 1NNC 2QWK
• 分子名称: neuraminidase, alpha-D-mannopyranose-(1-2)-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, 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: n9 neuraminidase, hydrolase, influenza, glycosylated protein, bcx-1812
• 由来する生物種: Influenza A virus
• 細胞内の位置: Virion membrane (By similarity): P03472
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46289.33

構造登録者

Smith, B.J.,McKimm-Breshkin, J.L.,McDonald, M.,Fernley, R.T.,Varghese, J.N.,Colman, P.M. (登録日: 2002-03-15, 公開日: 2002-05-29, 最終更新日: 2024-11-20)

主引用文献

Smith, B.J.,McKimm-Breshkin, J.L.,McDonald, M.,Fernley, R.T.,Varghese, J.N.,Colman, P.M.
Structural studies of the resistance of influenza virus neuramindase to inhibitors.
J.Med.Chem., 45:2207-2212, 2002

PubMed Abstract: Zanamivir and oseltamivir, specific inhibitors of influenza virus neuraminidase, have significantly different characteristics in resistance studies. In both cases resistance is known to arise through mutations in either the hemagglutinin or neuraminidase surface proteins. A new inhibitor under development by Biocryst Pharmaceuticals, BCX-1812, has both a guanidino group, as in zanamivir, and a bulky hydrophobic group, as in oseltamivir. Using influenza A/NWS/Tern/Australia/G70C/75 (H1N9), neuraminidase variants E119G and R292K have previously been selected by different inhibitors. The sensitivity of these variants to BCX-1812 has now been measured and found in both cases to be intermediate between those of zanamivir and oseltamivir. In addition, the X-ray crystal structures of the complexes of BCX-1812 with the wild type and the two mutant neuraminidases were determined. The ligand is bound in an identical manner in each structure, with a rearrangement of the side chain of E276 from its ligand-free position. A structural explanation of the mechanism of resistance of BCX-1812, relative to zanamivir and oseltamivir in particular, is provided.

PubMed: 12014958
DOI: 10.1021/jm010528u

実験手法

X-RAY DIFFRACTION (1.8 Å)