1l7f
From Proteopedia
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Crystal structure of influenza virus neuraminidase in complex with BCX-1812
Overview
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.
About this Structure
1L7F is a Single protein structure of sequence from Unidentified influenza virus with NAG, CA, BCZ and GOL as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
Reference
Structural studies of the resistance of influenza virus neuramindase to inhibitors., Smith BJ, McKimm-Breshkin JL, McDonald M, Fernley RT, Varghese JN, Colman PM, J Med Chem. 2002 May 23;45(11):2207-12. PMID:12014958
Page seeded by OCA on Tue Nov 20 20:20:42 2007
