An essential Trypanosoma brucei protein kinase: a functional analysis of regulation and the identification of inhibitors.

ABSTRACT:

Introduction

The protein serine/threonine kinase AEK1 is essential in the pathogenic stage of Trypanosoma brucei, the causative agent of African trypanosomiasis. AEK1 is a member of the AGC protein kinase family, although it is not closely related to a specific human AGC kinase. Our previous chemical genetic studies showed that targeted inhibition of AEK1 in parasites expressing analog-sensitive AEK1 blocked parasite growth and enhanced survival of infected mice.

Methods

To further validate AEK1 as a drug target, we used the chemical genetic system to determine the effect of a 24 hour loss of AEK1 activity on cell viability at the clonal level. A panel of 429 protein kinase inhibitors were screened against the wild-type protein for binding, using time-resolved fluorescence e

SUBMITTER: Parsons M 

PROVIDER: S-EPMC10720658 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature