9YC7
Plasmodium falciparum M17 aminopeptidase (PfA-M17) bound to inhibitor 3k (MIPS3415)
This is a non-PDB format compatible entry.
Summary for 9YC7
| Entry DOI | 10.2210/pdb9yc7/pdb |
| Descriptor | M17 leucyl aminopeptidase, ZINC ION, CARBONATE ION, ... (10 entities in total) |
| Functional Keywords | m17 aminopeptidase, aminopeptidase inhibitor, p. falciparum, malaria, hydrolase |
| Biological source | Plasmodium falciparum (malaria parasite P. falciparum) |
| Total number of polymer chains | 12 |
| Total formula weight | 715647.89 |
| Authors | Mansouri, M.,McGowan, S.,Webb, C.T. (deposition date: 2025-09-18, release date: 2026-01-28, Last modification date: 2026-02-04) |
| Primary citation | Mansouri, M.,De Paoli, A.,Giannangelo, C.,Chowdury, M.,Ngo, A.,Shackleford, D.M.,Webb, C.T.,Lowes, K.N.,Creek, D.J.,Charman, S.A.,Koning-Ward, T.F.,McGowan, S.,Scammells, P.J. Novel Scaffold Unlocks Potent Cross-Peptidase and Cross-Species Inhibitors as Promising Antimalarial Agents. J.Med.Chem., 69:1358-1386, 2026 Cited by PubMed Abstract: Malaria remains a global health burden and the emergence of parasite-resistance to frontline drugs highlights an urgent need for new therapeutics with novel mechanisms of action. Inhibiting aminopeptidases, in particular the M1 and M17 aminopeptidases (A-M1 and A-M17 respectively) has been shown to cause parasite death. In this study, both ligand-based and structure-based design strategies were utilized to identify novel scaffolds that act as dual inhibitors of these enzymes. Structural studies supported the improved activity showing strong hydrophobic and additional hydrogen interactions between the new cores and the S1 pocket of the enzymes. These inhibitors were highly effective against and , showing cross-peptidase and cross-species activity while also retaining activity against multidrug resistant strains. Progression to efficacy studies showed reduction in parasitaemia in mice infected with demonstrating encouraging prospects to develop suitable drug-like candidates for the treatment of malaria. PubMed: 41525497DOI: 10.1021/acs.jmedchem.5c02743 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.37 Å) |
Structure validation
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