9Y65
Plasmodium falciparum M1 aminopeptidase (PfA-M1) bound to inhibitor 3k (MIPS3415)
This is a non-PDB format compatible entry.
Summary for 9Y65
| Entry DOI | 10.2210/pdb9y65/pdb |
| Descriptor | Plasmodium falciparum M1 aminopeptidase (PfA-M1), DIMETHYL SULFOXIDE, N-[(1R)-2-(hydroxyamino)-2-oxo-1-(quinolin-7-yl)ethyl]-3,3-dimethylbutanamide, ... (8 entities in total) |
| Functional Keywords | m1 aminopeptidase, m1 aminopeptidase inhibitor, p. falciparum, malaria, hydrolase |
| Biological source | Plasmodium falciparum |
| Total number of polymer chains | 1 |
| Total formula weight | 127228.93 |
| Authors | Mansouri, M.,McGowan, S.,Webb, C.T. (deposition date: 2025-09-08, 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 (2.2 Å) |
Structure validation
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