3t8v: Difference between revisions
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[[ | ==A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases== | ||
<StructureSection load='3t8v' size='340' side='right' caption='[[3t8v]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</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> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ebg|3ebg]], [[3t8w|3t8w]]</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=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> | |||
</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: M1 alanyl-aminopeptidase]] | [[Category: M1 alanyl-aminopeptidase]] | ||
[[Category: Metallo-aminopeptidase]] | [[Category: Metallo-aminopeptidase]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
Revision as of 13:45, 9 December 2014
A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases
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