4x2t
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum== | |
| + | <StructureSection load='4x2t' size='340' side='right'caption='[[4x2t]], [[Resolution|resolution]] 2.73Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4x2t]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X2T 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]] 2.729Å</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=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TOD:(2S)-({(2R)-2-[(1S)-1-HYDROXY-2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}AMINO)(PHENYL)ETHANOIC+ACID'>TOD</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=4x2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x2t OCA], [https://pdbe.org/4x2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x2t RCSB], [https://www.ebi.ac.uk/pdbsum/4x2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x2t ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AMPL_PLAF7 AMPL_PLAF7] Aminopeptidase which preferentially cleaves leucine residues from the N-terminus of peptides (PubMed:17107951, PubMed:21844374, PubMed:22359643, PubMed:33536500, PubMed:34133730). Also, has some activity towards tryptophan and methionine and to a lesser extent towards phenylalanine (PubMed:17107951, PubMed:22359643, PubMed:34133730). Has very low activity or no activity towards the other amino acids (PubMed:17107951, PubMed:22359643, PubMed:34133730). In addition, cleaves the Cys-Gly dipeptide, probably as part of the glutathione regulation pathway; cleavage only occurs in the presence of Mn(2+) (PubMed:33303633). During the asexual blood stage, plays a role in the final step of host hemoglobin catabolism, by cleaving hemoglobin-derived oligopeptides providing a source of amino acids for the parasite protein synthesis and for the maintenance of osmotic homeostasis (PubMed:34133730). During the asexual blood stage, may also play a role during the ring-trophozoite transition (PubMed:21844374).<ref>PMID:17107951</ref> <ref>PMID:21844374</ref> <ref>PMID:22359643</ref> <ref>PMID:33303633</ref> <ref>PMID:33536500</ref> <ref>PMID:34133730</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | New antimalarial treatments are desperately required to face the spread of drug resistant parasites. Inhibition of metalloaminopeptidases PfA-M1 and PfA-M17 is a validated therapeutic strategy for treatment of Plasmodium falciparum malaria. Here we describe the crystal structures of PfA-M1 and PfA-M17 bound to chemotherapeutic agent Tosedostat. The inhibitor occupies the enzymes' putative product egress channels in addition to the substrate binding pockets; however, adopts different binding poses when bound to PfA-M1 and PfA-M17. These findings will be valuable for the continued development of selective inhibitors of PfA-M1 and PfA-M17. This article is protected by copyright. All rights reserved. | ||
| - | + | X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.,Drinkwater N, Bamert RS, Kannan Sivaraman K, Paiardini A, McGowan S Proteins. 2015 Feb 2. doi: 10.1002/prot.24771. PMID:25645579<ref>PMID:25645579</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Drinkwater | + | <div class="pdbe-citations 4x2t" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| + | ==See Also== | ||
| + | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Plasmodium falciparum 3D7]] | ||
| + | [[Category: Drinkwater N]] | ||
| + | [[Category: McGowan S]] | ||
Current revision
X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum
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