5w6t
From Proteopedia
Crystal structure of the A/Puerto Rico/8/1934 (H1N1) influenza virus hemagglutinin in complex with cyclic peptide CP151070 (P7)
Structural highlights
FunctionHEMA_I34A1 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 either through clathrin-dependent endocytosis or through 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.[HAMAP-Rule:MF_04072] Publication Abstract from PubMedInfluenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential new pandemics, emerging viruses, and constantly mutating circulating strains. We report here on design and structural characterization of potent peptidic inhibitors against influenza hemagglutinin (HA). The peptide design was based on complementarity determining region (CDR) loops of anti-HA human broadly neutralizing antibodies, FI6v3 and CR9114. The optimized peptides exhibit nanomolar affinity and neutralization against group 1 influenza A viruses including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH-induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate development of novel small molecule and peptide-based therapeutics against influenza virus. Potent peptidic fusion inhibitors of influenza virus.,Kadam RU, Juraszek J, Brandenburg B, Buyck C, Schepens WBG, Kesteleyn B, Stoops B, Vreeken R, Vermond J, Goutier W, Tang C, Vogels R, Friesen RHE, Goudsmit J, van Dongen MJP, Wilson IA Science. 2017 Sep 28. pii: eaan0516. doi: 10.1126/science.aan0516. PMID:28971971[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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