5W5S

Crystal structure of the A/Puerto Rico/8/1934 (H1N1) influenza virus hemagglutinin in complex with cyclic peptide CP141019 (P5)

Summary for 5W5S

• Entry DOI: 10.2210/pdb5w5s/pdb
• Related: 5w5u 5w6i 5w6r 5w6t 5w6u
• Descriptor: Hemagglutinin, ACE-PH8-ORN-LEU-GLU-TYR-ZCL-GLU-TRP-LEU-SER-BAL, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: glycoprotein, ectodomain, n-glycosylation, viral protein
• Biological source: Influenza A virus (strain A/Puerto Rico/8/1934 H1N1); More
• Total number of polymer chains: 3
• Total formula weight: 60152.24

Authors

Wilson, I.A.,Kadam, R.U. (deposition date: 2017-06-15, release date: 2017-10-04, Last modification date: 2023-11-15)

Primary citation

Kadam, R.U.,Juraszek, J.,Brandenburg, B.,Buyck, C.,Schepens, W.B.G.,Kesteleyn, B.,Stoops, B.,Vreeken, R.J.,Vermond, J.,Goutier, W.,Tang, C.,Vogels, R.,Friesen, R.H.E.,Goudsmit, J.,van Dongen, M.J.P.,Wilson, I.A.
Potent peptidic fusion inhibitors of influenza virus.
Science, 358:496-502, 2017

PubMed Abstract: Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 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 the development of new small molecule- and peptide-based therapeutics against influenza virus.

PubMed: 28971971
DOI: 10.1126/science.aan0516

Experimental method

X-RAY DIFFRACTION (2.284 Å)