1L7G: Crystal Structure Of E119g Mutant Influenza Virus Neuraminidase In Complex With Bcx-1812

Citation:
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.
PDB ID: 1L7GDownload
MMDB ID: 19599
PDB Deposition Date: 2002/3/15
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 1L7G: tetrameric; determined by author and by software (PISA,PQS)
Molecular Components in 1L7G
Label Count Molecule
Proteins (4 molecules)
4
Neuraminidase
Molecule annotation
Chemicals (36 molecules)
1
16
2
4
3
4
4
12
* Click molecule labels to explore molecular sequence information.

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