View source for 9yc0


==Plasmodium falciparum M17 aminopeptidase (PfA-M17) bound to inhibitor 3ab (MIPS3413)==
<StructureSection load='9yc0' size='340' side='right'caption='[[9yc0]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9yc0]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9YC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YC0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.37&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=A1CT4:N-[(1R)-1-(1,3-benzothiazol-5-yl)-2-(hydroxyamino)-2-oxoethyl]-3,3-dimethylbutanamide'>A1CT4</scene>, <scene name='pdbligand=A1CT5:N-[(1S)-1-(1,3-benzothiazol-5-yl)-2-(hydroxyamino)-2-oxoethyl]-3,3-dimethylbutanamide'>A1CT5</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9yc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9yc0 OCA], [https://pdbe.org/9yc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9yc0 RCSB], [https://www.ebi.ac.uk/pdbsum/9yc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9yc0 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 Plasmodium falciparum M1 and M17 aminopeptidases (PfA-M1 and PfA-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 Plasmodium vivax and Plasmodium berghei, showing cross-peptidase and cross-species activity while also retaining activity against multidrug resistant P. falciparum strains. Progression to in vivo efficacy studies showed reduction in parasitaemia in mice infected with P. berghei demonstrating encouraging prospects to develop suitable drug-like candidates for the treatment of malaria.

Novel Scaffold Unlocks Potent Cross-Peptidase and Cross-Species Inhibitors as Promising Antimalarial Agents.,Mansouri M, De Paoli A, Giannangelo C, Chowdury M, Ngo A, Shackleford DM, Webb CT, Lowes KN, Creek DJ, Charman SA, Koning-Ward TF, McGowan S, Scammells PJ J Med Chem. 2026 Jan 22;69(2):1358-1386. doi: 10.1021/acs.jmedchem.5c02743. Epub , 2026 Jan 12. PMID:41525497<ref>PMID:41525497</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9yc0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Mansouri M]]
[[Category: McGowan S]]
[[Category: Webb CT]]