Trypanosoma brucei: inhibition of cathepsin L is sufficient to kill bloodstream forms

Steverding, Dietmar, Rushworth, Stuart, Florea, Bogdan I. and Overkleeft, Herman S. (2020) Trypanosoma brucei: inhibition of cathepsin L is sufficient to kill bloodstream forms. Molecular and Biochemical Parasitology, 235. ISSN 0166-6851

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Abstract

The lysosomal cysteine protease activity of Trypanosoma brucei comprises a cathepsin B enzyme (TbCATB) and a cathepsin L enzyme (TbCATL). Inhibition of the cysteine protease activity is lethal to bloodstream-form trypanosomes but it was not entirely clear which of the two enzymes are essential for survival of the parasites. Here we show that the vinyl sulfone compound LU-102 selectively inhibits TbCATL without affecting TbCATB and the proteasomal trypsin-like activity within trypanosomes. Therefore, the trypanocidal activity displayed by LU-102 can be attributed solely to the inhibition of TbCATL demonstrating that this enzyme is essential to the survival of T. brucei.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 18 Nov 2019 13:30
Last Modified: 12 Jul 2020 23:54
URI: https://ueaeprints.uea.ac.uk/id/eprint/72990
DOI: 10.1016/j.molbiopara.2019.111246

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