Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00100111" target="_blank" >RIV/00216224:14740/17:00100111 - isvavai.cz</a>

Result on the web

<a href="http://science.sciencemag.org/content/355/6332/1416" target="_blank" >http://science.sciencemag.org/content/355/6332/1416</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/science.aal1807" target="_blank" >10.1126/science.aal1807</a>

Result language

angličtina

Original language name

Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Science

ISSN

0036-8075

e-ISSN

—

Volume of the periodical

355

Issue of the periodical within the volume

6332

Country of publishing house

US - UNITED STATES

Number of pages

5

Pages from-to

1416

UT code for WoS article

000397809500041

EID of the result in the Scopus database

2-s2.0-85016811904