5cbm: Difference between revisions
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==Crystal structure of PfA-M17 with virtual ligand inhibitor== | |||
<StructureSection load='5cbm' size='340' side='right'caption='[[5cbm]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5cbm]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_Vietnam_Oak-Knoll_(FVO) Plasmodium falciparum Vietnam Oak-Knoll (FVO)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CBM 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]] 2.3Å</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=4ZN:(2S)-2-{[(R)-[(R)-AMINO(PHENYL)METHYL](HYDROXY)PHOSPHORYL]METHYL}-4-METHYLPENTANOIC+ACID'>4ZN</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5cbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cbm OCA], [https://pdbe.org/5cbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cbm RCSB], [https://www.ebi.ac.uk/pdbsum/5cbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cbm ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A024V0B1_PLAFA A0A024V0B1_PLAFA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Plasmodium falciparum PfA-M1 and PfA-M17 metalloaminopeptidases are validated drug targets for the discovery of antimalarial agents. In order to identify dual inhibitors of both proteins, we developed a hierarchical virtual screening approach, followed by in vitro evaluation of the highest scoring hits. Starting from the ZINC database of purchasable compounds, sequential 3D-pharmacophore and molecular docking steps were applied to filter the virtual 'hits'. At the end of virtual screening, 12 compounds were chosen and tested against the in vitro aminopeptidase activity of both PfA-M1 and PfA-M17. Two molecules showed significant inhibitory activity (low micromolar/nanomolar range) against both proteins. Finally, the crystal structure of the most potent compound in complex with both PfA-M1 and PfA-M17 was solved, revealing the binding mode and validating our computational approach. | |||
Identification and Validation of a Potent Dual Inhibitor of the P. falciparum M1 and M17 Aminopeptidases Using Virtual Screening.,Ruggeri C, Drinkwater N, Sivaraman KK, Bamert RS, McGowan S, Paiardini A PLoS One. 2015 Sep 25;10(9):e0138957. doi: 10.1371/journal.pone.0138957., eCollection 2015. PMID:26406322<ref>PMID:26406322</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Drinkwater | <div class="pdbe-citations 5cbm" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Drinkwater N]] | |||
[[Category: McGowan S]] | |||
[[Category: Ruggeri C]] | |||
Latest revision as of 14:19, 10 January 2024
Crystal structure of PfA-M17 with virtual ligand inhibitorCrystal structure of PfA-M17 with virtual ligand inhibitor
Structural highlights
FunctionPublication Abstract from PubMedThe Plasmodium falciparum PfA-M1 and PfA-M17 metalloaminopeptidases are validated drug targets for the discovery of antimalarial agents. In order to identify dual inhibitors of both proteins, we developed a hierarchical virtual screening approach, followed by in vitro evaluation of the highest scoring hits. Starting from the ZINC database of purchasable compounds, sequential 3D-pharmacophore and molecular docking steps were applied to filter the virtual 'hits'. At the end of virtual screening, 12 compounds were chosen and tested against the in vitro aminopeptidase activity of both PfA-M1 and PfA-M17. Two molecules showed significant inhibitory activity (low micromolar/nanomolar range) against both proteins. Finally, the crystal structure of the most potent compound in complex with both PfA-M1 and PfA-M17 was solved, revealing the binding mode and validating our computational approach. Identification and Validation of a Potent Dual Inhibitor of the P. falciparum M1 and M17 Aminopeptidases Using Virtual Screening.,Ruggeri C, Drinkwater N, Sivaraman KK, Bamert RS, McGowan S, Paiardini A PLoS One. 2015 Sep 25;10(9):e0138957. doi: 10.1371/journal.pone.0138957., eCollection 2015. PMID:26406322[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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