5t6n | pdb_00005t6n

Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin in complex with the antiviral drug arbidol

spinqualitylabelsall models 5t6n, resolution 2.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5t6n is a 6 chain structure with sequence from Influenza A virus (A/Hong Kong/1/1968(H3N2)) and Influenza A virus (A/nt/60/1968(H3N2)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.541Å Ligands: 75U, BMA, GOL, MAN, NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HEMA_I68A6 Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore. Publication Abstract from PubMed The broad-spectrum antiviral drug Arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (HA) fusion machinery. However, the structural basis of the mechanism underlying fusion inhibition by Arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. We determined crystal structures of Arbidol in complex with influenza virus HA from pandemic 1968 H3N2 and recent 2013 H7N9 viruses. Arbidol binds in a hydrophobic cavity in the HA trimer stem at the interface between two protomers. This cavity is distal to the conserved epitope targeted by broadly neutralizing stem antibodies and is approximately 16 A from the fusion peptide. Arbidol primarily makes hydrophobic interactions with the binding site but also induces some conformational rearrangements to form a network of inter- and intraprotomer salt bridges. By functioning as molecular glue, Arbidol stabilizes the prefusion conformation of HA that inhibits the large conformational rearrangements associated with membrane fusion in the low pH of the endosome. This unique binding mode compared with the small-molecule inhibitors of other class I fusion proteins enhances our understanding of how small molecules can function as fusion inhibitors and guides the development of broad-spectrum therapeutics against influenza virus. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol.,Kadam RU, Wilson IA Proc Natl Acad Sci U S A. 2016 Dec 21. pii: 201617020. doi:, 10.1073/pnas.1617020114. PMID:28003465 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hemagglutinin 3D structures

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