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PDBsum entry 1l7h

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Hydrolase PDB id
1l7h
Jmol
Contents
Protein chain
388 a.a. *
Ligands
NAG-NAG-BMA-MAN-
MAN-MAN-MAN
NAG-NAG
NAG
BCZ
GOL ×3
Metals
_CA ×3
Waters ×566
* Residue conservation analysis

References listed in PDB file
Key reference
Title Structural studies of the resistance of influenza virus neuramindase to inhibitors.
Authors B.J.Smith, J.L.Mckimm-Breshkin, M.Mcdonald, R.T.Fernley, J.N.Varghese, P.M.Colman.
Ref. J Med Chem, 2002, 45, 2207-2212. [DOI no: 10.1021/jm010528u]
PubMed id 12014958
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.
Secondary reference #1
Title Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase.
Authors J.N.Varghese, P.W.Smith, S.L.Sollis, T.J.Blick, A.Sahasrabudhe, J.L.Mckimm-Breschkin, P.M.Colman.
Ref. Structure, 1998, 6, 735-746. [DOI no: 10.1016/S0969-2126(98)00075-6]
PubMed id 9655825
Full text Abstract
Figure 1.
Figure 1. The chemical structures of influenza neuraminidase inhibitors: 1, sialic acid (N-acetylneuraminic acid (Neu5Ac)); 2, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en); 3, 4-amino-Neu5Ac2en; 4, Zanamivir, 4-guanidino-Neu5Ac2en; 5, 5-N-acetyl-4-guanidino-6-methyl(propyl) carboxamide-4,5-dihydro-2H-pyran-2-carboxylic acid; 6, 5-N-acetyl-4-amino-6-diethyl carboxamide-4,5-dihydro-2H-pyran-2-carboxylic acid; and 7, GS4071, 4-N-acetyl-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid.
The above figure is reproduced from the cited reference with permission from Cell Press
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