This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
3t8w
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==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
| |||||||||||
