Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation

Abstract

Current chemotherapies against trypanosomiasis are beset with diverse challenges, a situation which underscores the numerous research efforts aimed at finding newer and effective treatments. Arginine kinase of trypanosome has been validated as target for drug development against trypanosomiasis. The present study investigated the interaction between a recombinant form of the arginine kinase (rTbAK) of trypanosome and gallotannin. The interaction between gallotannin and recombinant arginine kinase of Trypanosoma brucei caused significant decrease of enzyme activity. Kinetic analysis revealed the interaction to be of noncompetitive inhibition. Further thermodynamic analysis showed that the interaction between gallotannin and the recombinant arginine kinase was nonspontaneous and involved hydrophobic forces. The K sv values and the FRET analysis suggest that static quenching of fluorescence intensity by gallotannin was static. Data revealed inhibitory interactions between gallotannin and rTbAK of trypanosome. Although the mechanism of inhibition is not clear yet, molecular docking studies are ongoing to clearly define the inhibitory interactions between the gallotannin and rTbAK. The knowledge of such binding properties would enrich development of selective inhibitors for the arginine kinase of Trypanosoma brucei.

Apoferritin and Apoferritin-Capped Metal Nanoparticles Inhibit Arginine Kinase of Trypanosoma brucei

“…Our findings indicate that the apoferritin-nanoparticles (Ag, Au and Pt) or apoferritin interacted with arginine kinase of T. brucei in a way that appreciably decreased the enzyme activity. Apoferritin reduced the activity of the arginine kinase of T. brucei by >90% while the apoferritin-nanoparticles decreased the relative activity of the enzyme by >70%, confirming earlier reports [ 17 , 18 , 19 ]. Due to the small sizes of these particles, both apoferritin and apoferritin-nanoparticles may offer opportunities for the selective inhibition of arginine kinase of T. brucei .…”

“…Several investigations have shown that the arginine kinase of T. brucei could be a target for the development of newer trypanocides [ 9 , 10 , 15 , 16 , 17 , 18 , 19 , 24 , 25 ]. The arginine kinase of T. brucei is an attractive drug target simply because it is not only critical to the survival of bloodstream forms of the parasite particularly under stressful conditions, but the enzyme is completely absent in human hosts [ 16 ].…”

“…The protein concentration was estimated by the Bradford method [ 36 ], while the enzymatic activity of T. brucei arginine kinase was confirmed as described elsewhere [ 17 , 18 , 19 ]. For the determination of enzyme activity, the assay medium contained Tris-HCl buffer (100 mM, pH 8.6), L-arginine (2 mM), ATP disodium salt (0.5 mM), mercaptoethanol (10 mM), magnesium sulfate (200 mM) and 0.002 mmol of the enzyme.…”

“…Previously, we reported that polyphenol-capped nanoparticles and gallotannin strongly inhibited a recombinant form of arginine kinase [ 17 , 18 , 19 ]. Specifically, nanoparticles are of interest because of their small sizes as well as the large surface to area ratio.…”

Corrigendum to “Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation”

“…In the article titled “Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei : Thermodynamic and Spectrofluorimetric Evaluation” [ 1 ], there were a typo in Equation (7), where the denominator K2 should be corrected to K1, and an error in Table 2, where the values for Δ H, Δ S, and Δ G were incorrectly calculated. The equation and table are corrected as follows: …”