4gb1

Synthesis and Evaluation of Novel 3-C-alkylated-Neu5Ac2en Derivatives as Probes of Influenza Virus Sialidase 150-loop flexibility

spinqualitylabelsall models 4gb1, resolution 2.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gb1 is a 1 chain structure with sequence from Influenza A virus (A/duck/Ukraine/1/1963(H3N8)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.62Å Ligands: 0LP, CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NRAM_I63A3 Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication. Publication Abstract from PubMed Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility. Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility.,Rudrawar S, Kerry PS, Rameix-Welti MA, Maggioni A, Dyason JC, Rose FJ, van der Werf S, Thomson RJ, Naffakh N, Russell RJ, von Itzstein M Org Biomol Chem. 2012 Sep 14. PMID:22976385 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Neuraminidase 3D structures

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