5MMC
Trypanosoma brucei Pex14 N-terminal domain
Summary for 5MMC
| Entry DOI | 10.2210/pdb5mmc/pdb |
| NMR Information | BMRB: 34073 |
| Descriptor | Peroxin 14 (1 entity in total) |
| Functional Keywords | peroxin 14, pex14, trypanosoma, peroxisome, signaling protein |
| Biological source | Trypanosoma brucei brucei |
| Total number of polymer chains | 1 |
| Total formula weight | 8021.19 |
| Authors | Emmanouilidis, L.,Tripsianes, K.,Sattler, M. (deposition date: 2016-12-09, release date: 2017-03-08, Last modification date: 2024-05-15) |
| Primary citation | Dawidowski, M.,Emmanouilidis, L.,Kalel, V.C.,Tripsianes, K.,Schorpp, K.,Hadian, K.,Kaiser, M.,Maser, P.,Kolonko, M.,Tanghe, S.,Rodriguez, A.,Schliebs, W.,Erdmann, R.,Sattler, M.,Popowicz, G.M. Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites. Science, 355:1416-1420, 2017 Cited by PubMed Abstract: The parasitic protists of the 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 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 suitable for the development of new therapies against trypanosomiases and provide the structural basis for their development. PubMed: 28360328DOI: 10.1126/science.aal1807 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
