4zw3
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4zw3 is ON HOLD Authors: Drinkwater, N., McGowan, S. Description: X-ray crystal structure of PfA-M1 in complex with hydroxamic acid-based inhibitor...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==X-ray crystal structure of PfA-M1 in complex with hydroxamic acid-based inhibitor 9b== | |
| + | <StructureSection load='4zw3' size='340' side='right'caption='[[4zw3]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4zw3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_FcB1/Columbia Plasmodium falciparum FcB1/Columbia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZW3 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4S9:TERT-BUTYL+[(1S)-1-(4-BROMOPHENYL)-2-(HYDROXYAMINO)-2-OXOETHYL]CARBAMATE'>4S9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4zw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zw3 OCA], [https://pdbe.org/4zw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zw3 RCSB], [https://www.ebi.ac.uk/pdbsum/4zw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zw3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AMP1_PLAFQ AMP1_PLAFQ] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.<ref>PMID:12166515</ref> <ref>PMID:19196988</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Malaria remains a global health problem, and though international efforts for treatment and eradication have made some headway, the emergence of drug-resistant parasites threatens this progress. Antimalarial therapeutics acting via novel mechanisms are urgently required. Plasmodium falciparum M1 and M17 are neutral aminopeptidases which are essential for parasite growth and development. Previous work in our group has identified inhibitors capable of dual inhibition of PfA-M1 and PfA-M17, and revealed further regions within the protease S1 pockets that could be exploited in the development of ligands with improved inhibitory activity. Herein, we report the structure-based design and synthesis of novel hydroxamic acid analogues that are capable of potent inhibition of both PfA-M1 and PfA-M17. Furthermore, the developed compounds potently inhibit Pf growth in culture, including the multi-drug resistant strain Dd2. The ongoing development of dual PfA-M1/PfA-M17 inhibitors continues to be an attractive strategy for the design of novel antimalarial therapeutics. | ||
| - | + | Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions.,Drinkwater N, Vinh NB, Mistry SN, Bamert RS, Ruggeri C, Holleran JP, Loganathan S, Paiardini A, Charman SA, Powell AK, Avery VM, McGowan S, Scammells PJ Eur J Med Chem. 2016 Mar 3;110:43-64. doi: 10.1016/j.ejmech.2016.01.015. Epub, 2016 Jan 13. PMID:26807544<ref>PMID:26807544</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Drinkwater | + | <div class="pdbe-citations 4zw3" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| + | ==See Also== | ||
| + | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Plasmodium falciparum FcB1/Columbia]] | ||
| + | [[Category: Drinkwater N]] | ||
| + | [[Category: McGowan S]] | ||
Current revision
X-ray crystal structure of PfA-M1 in complex with hydroxamic acid-based inhibitor 9b
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