Pseudoirreversible slow-binding inhibition of trypanothione reductase by a protein-protein interaction disruptor.

ABSTRACT:

Background and purpose

Peptide P4 was described as a dimerization disruptor of trypanothione reductase (TryR), a homodimeric enzyme essential for survival of trypanosomatids. Determination of the true inhibitory constant (K_i ) for P4 was not achieved because reaction rates continuously decreased with time, even when substrate concentration was kept constant. The aim of this study was to find a suitable kinetic model that could allow characterization of the complex pattern of TryR inhibition caused by P4.

Experimental approach

After showing the slow-binding and pseudoirreversible activity of P4 against Leishmania infantum trypanothione reductase (Li-TryR), analysis of the curvatures of the reaction progress curves at different inhibitor concentrations allowed us to

SUBMITTER: de Lucio H 

PROVIDER: S-EPMC7588817 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature