3t8v

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==A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases==
==A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases==
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<StructureSection load='3t8v' size='340' side='right' caption='[[3t8v]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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<StructureSection load='3t8v' size='340' side='right'caption='[[3t8v]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3t8v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T8V FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3t8v]] 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=3T8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T8V FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTJ:N-[(2-{2-[(N-{(2S,3R)-3-AMINO-4-[4-(BENZYLOXY)PHENYL]-2-HYDROXYBUTANOYL}-L-ALANYL)AMINO]ETHOXY}ETHOXY)ACETYL]-4-BENZOYL-L-PHENYLALANYL-N~6~-HEX-5-YNOYLLYSINAMIDE'>BTJ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ebg|3ebg]], [[3t8w|3t8w]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTJ:N-[(2-{2-[(N-{(2S,3R)-3-AMINO-4-[4-(BENZYLOXY)PHENYL]-2-HYDROXYBUTANOYL}-L-ALANYL)AMINO]ETHOXY}ETHOXY)ACETYL]-4-BENZOYL-L-PHENYLALANYL-N~6~-HEX-5-YNOYLLYSINAMIDE'>BTJ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3t8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t8v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t8v RCSB], [http://www.ebi.ac.uk/pdbsum/3t8v PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3t8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t8v OCA], [https://pdbe.org/3t8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t8v RCSB], [https://www.ebi.ac.uk/pdbsum/3t8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t8v ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. Peptidases are a promising class of drug targets and perform several important roles during the Plasmodium falciparum erythrocytic life cycle. Herein, we report a multidisciplinary effort combining activity-based protein profiling, biochemical, and peptidomic approaches to functionally analyze two genetically essential P. falciparum metallo-aminopeptidases (MAPs), PfA-M1 and Pf-LAP. Through the synthesis of a suite of activity-based probes (ABPs) based on the general MAP inhibitor scaffold, bestatin, we generated specific ABPs for these two enzymes. Specific inhibition of PfA-M1 caused swelling of the parasite digestive vacuole and prevented proteolysis of hemoglobin (Hb)-derived oligopeptides, likely starving the parasite resulting in death. In contrast, inhibition of Pf-LAP was lethal to parasites early in the life cycle, prior to the onset of Hb degradation suggesting that Pf-LAP has an essential role outside of Hb digestion.
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Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases.,Harbut MB, Velmourougane G, Dalal S, Reiss G, Whisstock JC, Onder O, Brisson D, McGowan S, Klemba M, Greenbaum DC Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):E526-34. Epub 2011 Aug 15. PMID:21844374<ref>PMID:21844374</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Aminopeptidase|Aminopeptidase]]
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*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Plasmodium falciparum]]
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[[Category: Large Structures]]
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[[Category: Greebaum, D C]]
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[[Category: Plasmodium falciparum FcB1/Columbia]]
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[[Category: Klemba, M]]
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[[Category: Greebaum DC]]
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[[Category: McGowan, S]]
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[[Category: Klemba M]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: McGowan S]]
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[[Category: M1 alanyl-aminopeptidase]]
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[[Category: Metallo-aminopeptidase]]
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[[Category: Protease]]
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Current revision

A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases

PDB ID 3t8v

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