Abstract
Cysteine peptidases have been implicated in the development and pathogenesis of Eimeria. We have identified a single copy cathepsin B-like cysteine peptidase (EtCatB) gene in the genome database of Eimeria tenella. Molecular modeling of the predicted protein suggested that it differs significantly from host enzymes and could be a good drug target. EtCatB was expressed and secreted as a soluble, active, glycosylated mature enzyme from Pichia pastoris. Biochemical characterisation of the recombinant enzyme confirmed that it is cathepsin B-like. Screening of a focused library against the enzyme identified three inhibitors (a nitrile, a thiosemicarbazone and an oxazolon) that can be used as leads for novel drug discovery against Eimeria. The oxazolone scaffold is a novel cysteine peptidase inhibitor, it may thus find widespread use.
Original language | English |
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Journal | Antimicrobial Agents and Chemotherapy |
DOIs | |
Publication status | Published - 2011 |
Keywords
- lead compounds
- cathepsin B-like enzyme
- Eimeria tenella