5l87
From Proteopedia
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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=5l87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l87 OCA], [http://pdbe.org/5l87 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l87 RCSB], [http://www.ebi.ac.uk/pdbsum/5l87 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l87 ProSAT]</span></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=5l87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l87 OCA], [http://pdbe.org/5l87 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l87 RCSB], [http://www.ebi.ac.uk/pdbsum/5l87 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l87 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The parasitic protists of the Trypanosoma genus infect humans and domestic mammals, causing severe mortality and huge economic losses. The most threatening trypanosomiasis is Chagas disease, affecting up to 12 million people in the Americas. We report a way to selectively kill Trypanosoma by blocking glycosomal/peroxisomal import that depends on the PEX14-PEX5 protein-protein interaction. We developed small molecules that efficiently disrupt the PEX14-PEX5 interaction. This results in mislocalization of glycosomal enzymes, causing metabolic catastrophe, and it kills the parasite. High-resolution x-ray structures and nuclear magnetic resonance data enabled the efficient design of inhibitors with trypanocidal activities comparable to approved medications. These results identify PEX14 as an "Achilles' heel" of the Trypanosoma suitable for the development of new therapies against trypanosomiases and provide the structural basis for their development. | ||
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| + | Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites.,Dawidowski M, Emmanouilidis L, Kalel VC, Tripsianes K, Schorpp K, Hadian K, Kaiser M, Maser P, Kolonko M, Tanghe S, Rodriguez A, Schliebs W, Erdmann R, Sattler M, Popowicz GM Science. 2017 Mar 31;355(6332):1416-1420. doi: 10.1126/science.aal1807. PMID:28360328<ref>PMID:28360328</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5l87" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 05:02, 12 April 2017
Targeting the PEX14-PEX5 interaction by small molecules provides novel therapeutic routes to treat trypanosomiases.
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