9y65: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 9y65 is ~~ON HOLD until Paper~~ Publication

==Plasmodium falciparum M1 aminopeptidase (PfA-M1) bound to inhibitor 3k (MIPS3415)==

== Structural highlights ==

<table><tr><td colspan='2'>[[9y65]] is a 1 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=9Y65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Y65 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]] 2.2Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CTH:N-[(1R)-2-(hydroxyamino)-2-oxo-1-(quinolin-7-yl)ethyl]-3,3-dimethylbutanamide'>A1CTH</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=9y65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9y65 OCA], [https://pdbe.org/9y65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9y65 RCSB], [https://www.ebi.ac.uk/pdbsum/9y65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9y65 ProSAT]</span></td></tr>

</table>

== 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.

~~Authors:~~ Mansouri, M., ~~McGowan~~, S., Webb, C.T.

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>

~~Description~~: ~~Plasmodium falciparum M1 aminopeptidase (PfA-M1) bound to inhibitor 3k (MIPS3415)~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: ~~Mcgowan, S~~]]

[[Category: Mansouri, M]]

== References ==

[[Category: Webb~~, C.T~~]]

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Plasmodium falciparum]]

[[Category: Mansouri M]]

[[Category: McGowan S]]

[[Category: Webb CT]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9y65 is ON HOLD  until Paper Publication
+==Plasmodium falciparum M1 aminopeptidase (PfA-M1) bound to inhibitor 3k (MIPS3415)==
+<StructureSection load='9y65' size='340' side='right'caption='[[9y65]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9y65]] is a 1 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=9Y65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Y65 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CTH:N-[(1R)-2-(hydroxyamino)-2-oxo-1-(quinolin-7-yl)ethyl]-3,3-dimethylbutanamide'>A1CTH</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=9y65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9y65 OCA], [https://pdbe.org/9y65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9y65 RCSB], [https://www.ebi.ac.uk/pdbsum/9y65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9y65 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.
-Authors: Mansouri, M., McGowan, S., Webb, C.T.
+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>
-Description: Plasmodium falciparum M1 aminopeptidase (PfA-M1) bound to inhibitor 3k (MIPS3415)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Mcgowan, S]]
+<div class="pdbe-citations 9y65" style="background-color:#fffaf0;"></div>
-[[Category: Mansouri, M]]
+== References ==
-[[Category: Webb, C.T]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Plasmodium falciparum]]
+[[Category: Mansouri M]]
+[[Category: McGowan S]]
+[[Category: Webb CT]]