9XAO
Spatial structure of the antimicrobial peptide Ap9
Summary for 9XAO
| Entry DOI | 10.2210/pdb9xao/pdb |
| Descriptor | antimicrobial peptide Ap9 (1 entity in total) |
| Functional Keywords | antibiotic, antimicrobial peptides, protein |
| Biological source | Abarenicola pacifica |
| Total number of polymer chains | 1 |
| Total formula weight | 2487.93 |
| Authors | Safronova, V.N.,Lushpa, V.A.,Panteleev, P.V.,Ovchinnikova, T.V.,Bocharov, E.V. (deposition date: 2025-10-22, release date: 2026-06-10) |
| Primary citation | Safronova, V.N.,Lushpa, V.A.,Shipunova, V.O.,Volovik, M.V.,Dobrochaeva, K.L.,Kruglikov, R.N.,Bolosov, I.A.,Dashevskii, D.E.,Mishin, A.V.,Batishchev, O.V.,Korobova, O.V.,Borzilov, A.I.,Slashcheva, G.A.,Dyachenko, I.A.,Bocharov, E.V.,Panteleev, P.V.,Ovchinnikova, T.V. Marine Antimicrobial Peptide as a Promising Alternative to Polymyxin B. Mar Drugs, 24:-, 2026 Cited by PubMed Abstract: The rise in antimicrobial resistance represents a significant challenge to global health. The reason partially lies in an inappropriate use of conventional antibiotics and the subsequent rapid spread of multidrug-resistant pathogen strains. This emergency requires an urgent search for conceptually new antimicrobial agents. A viable alternative to conventional antibiotics is antimicrobial peptides (AMPs), which are ribosomally synthesized molecules with considerable potential as next-generation anti-infectious therapeutics. Previously, we have reported on the β-hairpin peptide Ap9, an analog of abarenicin from the marine polychaeta , with potent activity against key Gram-negative pathogens. Here, it is shown that Ap9 acts in a manner resembling polymyxin B, namely via interaction with lipopolysaccharide (LPS), and retains its activity against polymyxin-resistant isolates without observed cross-resistance, and causes insignificant damage in cytoplasmic membrane at bactericidal concentrations. NMR spectroscopy reveals that LPS binding induces a conformational rearrangement of Ap9, its dimer formation, and local structural remodeling of the peptide region (residues 8-12) into 3-helix. Bacterial resistance to Ap9 was found to be relatively low with a reduced susceptibility associated with infrequent genetic alterations, such as the mutation in or the deletion in . Furthermore, Ap9 demonstrates a favorable tolerability, a wider therapeutic window than that of polymyxin B, and a sufficiently long half-life through the systemic use, as well as in vivo efficacy in murine models of Gram-negative infections, including sepsis caused by the -harboring strain. The obtained results point to Ap9 as a promising candidate for further preclinical studies aimed at development of an alternative to polymyxins. PubMed: 42188290DOI: 10.3390/md24050154 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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