|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Trypanosoma brucei Pex14 N-terminal domain== | | ==Trypanosoma brucei Pex14 N-terminal domain== |
| - | <StructureSection load='5mmc' size='340' side='right'caption='[[5mmc]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5mmc' size='340' side='right'caption='[[5mmc]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mmc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybb Trybb]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MMC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mmc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MMC FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PEX14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5702 TRYBB])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=5mmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mmc OCA], [http://pdbe.org/5mmc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mmc RCSB], [http://www.ebi.ac.uk/pdbsum/5mmc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mmc 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=5mmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mmc OCA], [https://pdbe.org/5mmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mmc RCSB], [https://www.ebi.ac.uk/pdbsum/5mmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mmc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q8IEW2_TRYBB Q8IEW2_TRYBB] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 23: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trybb]] | + | [[Category: Trypanosoma brucei brucei]] |
| - | [[Category: Emmanouilidis, L]] | + | [[Category: Emmanouilidis L]] |
| - | [[Category: Sattler, M]] | + | [[Category: Sattler M]] |
| - | [[Category: Tripsianes, K]] | + | [[Category: Tripsianes K]] |
| - | [[Category: Peroxin 14]]
| + | |
| - | [[Category: Peroxisome]]
| + | |
| - | [[Category: Pex14]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Trypanosoma]]
| + | |
| Structural highlights
Function
Q8IEW2_TRYBB
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites. Science. 2017 Mar 31;355(6332):1416-1420. doi: 10.1126/science.aal1807. PMID:28360328 doi:http://dx.doi.org/10.1126/science.aal1807
|
