Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 2.
doi: 10.2174/1573406416666200403074742. Online ahead of print.

The Interaction of Schistosoma Japonicum Glutathione Transferase With Cibacron Blue 3GA and Its Fragments

Affiliations

The Interaction of Schistosoma Japonicum Glutathione Transferase With Cibacron Blue 3GA and Its Fragments

Michalis Platis et al. Med Chem. .

Abstract

Background: The 26kDa glutathione transferase (GST, EC 2.5.1.18) from Schistosoma japonicum (SjGST) is recognized as the major detoxification enzyme of S. japonicum, a pathogenic helminth causing schistosomiasis.

Objective: In the present study, the interaction of the chlorotriazine dye Cibacron blue 3GA (CB3GA) and its structural analogues with SjGST was investigated. The work aimed to shine light on the non-substrate ligand-binding properties of the enzyme.

Methods: Kinetic inhibition analysis, affinity labelling experiments and molecular modelling studies were employed.

Results: The results showed that CB3GA is a potent inhibitor (IC50 0.057 ± 0.003μM) towards SjGST. The enzyme was specifically and irreversibly inactivated by the dichlorotriazine-analogue of CB3GA (IC50 0.190 ± 0.024 μM), following a biphasic pseudo-first-order saturation kinetics with approximately 1 mol of inhibitor per mol of dimeric enzyme being incorporated. All other monochlorotriazine analogues behave as reversible inhibitors with lower inhibition potency (IC50 5.2-82.3 μM). Kinetic inhibition studies together with molecular modelling and molecular dynamics simulations established that the CB3GA binding site overlaps both the G- and H-sites. Both hydrophobic/polar interactions as well as steric effects have decisive roles in determining the inhibitory strength of CB3GA and its analogues.

Conclusion: The results of the present study might be useful in future drug design and development efforts towards SjGST.

Keywords: Affinity labelling; Cibacron Blue 3GA; Schistosoma japonicum; Schistosomiasis; Structure-guided drug design; Triazine dyes..

Similar articles

See all similar articles

LinkOut - more resources

Feedback