9PHT
Crystal structure of the A/Vietnam/1203/2004 (H5N1) influenza virus hemagglutinin in complex with fusion inhibitor cyclic peptide CP141085 (CP1)
Summary for 9PHT
| Entry DOI | 10.2210/pdb9pht/pdb |
| Descriptor | Hemagglutinin, cyclic peptide CP141085, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | influenza virus, hemagglutinin, glycoprotein, n-glycosylation, viral protein |
| Biological source | Influenza A virus (A/Viet Nam/1203/2004(H5N1)) More |
| Total number of polymer chains | 3 |
| Total formula weight | 60733.08 |
| Authors | Kadam, R.U.,Wilson, I.A. (deposition date: 2025-07-09, release date: 2025-12-24, Last modification date: 2025-12-31) |
| Primary citation | Kadam, R.U.,Juraszek, J.,Brandenburg, B.,Garg, D.,Zhu, X.,Jongeneelen, M.,Schepens, W.B.G.,Stoops, B.,Vermond, J.,Goutier, W.,Tang, C.,Blokland, S.,Vogels, R.,Friesen, R.H.E.,van Dongen, M.J.P.,Wilson, I.A. V H H antibody loop guides design of a synthetic macrocyclic peptide that potently blocks influenza virus membrane fusion. Npj Viruses, 3:83-83, 2025 Cited by PubMed Abstract: Miniaturizing biologically complex structural motifs to produce synthetic functional mimetics holds significant promise for development of new therapeutic modalities. Here, we demonstrate a unique approach using the key binding loop of the single variable domain of a heavy chain (VH) llama antibody as a starting point for peptide design. VH antibodies of camelids and sharks generally have longer, but more ligand-efficient complementarity determining region 3 (CDR3) loops and are relatively stable structures. We harnessed these attributes as templates for design of a series of synthetic macrocyclic peptides. The designed peptides exhibit nanomolar binding to influenza hemagglutinin (HA) and heterosubtypic in vitro neutralization breadth against influenza A viruses by inhibiting the low pH mediated HA conformational changes that lead to membrane fusion. X-ray structures of peptide-HA complexes reveal high structural mimicry with the parent VH antibody. One such macrocycle peptide candidate is promising for further development of broad protection against influenza A group 1 viruses. PubMed: 41413306DOI: 10.1038/s44298-025-00166-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.76 Å) |
Structure validation
Download full validation report
