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3t8w

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Current revision (08:37, 20 March 2024) (edit) (undo)
 
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<StructureSection load='3t8w' size='340' side='right'caption='[[3t8w]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='3t8w' size='340' side='right'caption='[[3t8w]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3t8w]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T8W FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3t8w]] 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=3T8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T8W FirstGlance]. <br>
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</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=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=DGZ:N-((2R,3S,6S,18S,21S)-2-AMINO-18-(4-BENZOYLBENZYL)-21-CARBAMOYL-3-HYDROXY-6-(NAPHTHALEN-2-YLMETHYL)-4,7,16,19-TETRAOXO-1-PHENYL-11,14-DIOXA-5,8,17,20-TETRAAZAPENTACOSAN-25-YL)HEX-5-YNAMIDE'>DGZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t8v|3t8v]], [[3kqx|3kqx]]</div></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=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=DGZ:N-((2R,3S,6S,18S,21S)-2-AMINO-18-(4-BENZOYLBENZYL)-21-CARBAMOYL-3-HYDROXY-6-(NAPHTHALEN-2-YLMETHYL)-4,7,16,19-TETRAOXO-1-PHENYL-11,14-DIOXA-5,8,17,20-TETRAAZAPENTACOSAN-25-YL)HEX-5-YNAMIDE'>DGZ</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=3t8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t8w OCA], [https://pdbe.org/3t8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t8w RCSB], [https://www.ebi.ac.uk/pdbsum/3t8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t8w ProSAT]</span></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=3t8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t8w OCA], [https://pdbe.org/3t8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t8w RCSB], [https://www.ebi.ac.uk/pdbsum/3t8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t8w ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q8IL11_PLAF7 Q8IL11_PLAF7]
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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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<div class="pdbe-citations 3t8w" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Plaf7]]
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[[Category: Plasmodium falciparum 3D7]]
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[[Category: Greebaum, D C]]
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[[Category: Greebaum DC]]
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[[Category: Klemba, M]]
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[[Category: Klemba M]]
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[[Category: McGowan, S]]
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[[Category: McGowan S]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: M17-leucyl 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 3t8w

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