3k3a

Crystal Structure of B/Perth Neuraminidase D197E mutant in complex with Oseltamivir

spinqualitylabelsall models 3k3a, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3k3a is a 16 chain structure with sequence from Influenza B virus (B/Perth/211/2001). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: CA, G39, NAG, YT3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q3S340_9INFB Publication Abstract from PubMed We have identified a virus, B/Perth/211/2001, with a spontaneous mutation, D197E in the neuraminidase (NA), which confers cross-resistance to all NA inhibitors. We analyzed enzyme properties of the D197 and E197 NAs and compared these to a D197N NA, known to arise after oseltamivir treatment. Zanamivir and peramivir bound slowly to the wild type NA, but binding of oseltamivir was more rapid. The D197E/N mutations resulted in faster binding of all three inhibitors. Analysis of the crystal structures of D197 and E197 NAs with and without inhibitors showed that the D197E mutation compromised the interaction of neighboring R150 with the N-acetyl group, common to the substrate sialic acid and all NA inhibitors. Although rotation of the E275 in the NA active site occurs upon binding peramivir in both the D197 and E197 NAs, this does not occur upon binding oseltamivir in the E197 NA. Lack of the E275 rotation would also account for the loss of slow binding and the partial resistance of influenza B wild type NAs to oseltamivir. Structural and Functional Basis of Resistance to Neuraminidase Inhibitors of Influenza B Viruses.,Oakley AJ, Barrett S, Peat TS, Newman J, Streltsov VA, Waddington L, Saito T, Tashiro M, McKimm-Breschkin JL J Med Chem. 2010 Aug 9. PMID:20695427 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Neuraminidase 3D structures

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