3t8w
From Proteopedia
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| - | + | ==A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases== | |
| - | + | <StructureSection load='3t8w' size='340' side='right' caption='[[3t8w]], [[Resolution|resolution]] 2.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3t8w]] is a 12 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=3T8W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T8W FirstGlance]. <br> | |
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t8v|3t8v]], [[3kqx|3kqx]]</td></tr> | ||
| + | <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=3t8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t8w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t8w RCSB], [http://www.ebi.ac.uk/pdbsum/3t8w PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Aminopeptidase|Aminopeptidase]] | *[[Aminopeptidase|Aminopeptidase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
| - | [[Category: Greebaum, D C | + | [[Category: Greebaum, D C]] |
| - | [[Category: Klemba, M | + | [[Category: Klemba, M]] |
| - | [[Category: McGowan, S | + | [[Category: McGowan, S]] |
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: M17-leucyl aminopeptidase]] | [[Category: M17-leucyl aminopeptidase]] | ||
[[Category: Metallo-aminopeptidase]] | [[Category: Metallo-aminopeptidase]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
Revision as of 08:43, 18 December 2014
A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases
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