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Updated: Aug 29, 2025
Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Elucidating structure and dynamics of glutathione S-transferase from Rhipicephalus (Boophilus) microplus
Warin Rangubpit1,2, Eukote Suwan1, Danai Sangthong1
1Department of Veterinary Technology, Faculty of Veterinary Technology, Kasetsart University, Bangkok, Thailand.
Abstract:
Rhipicephalus (Boophilus) microplus is tick parasite that affects the cattle industry worldwide. In R. (B.) microplus, acaricide resistance develops rapidly against many commercial acaricides. One of main resistance strategies is to enhance the metabolic detoxification mediated by R. (B.) microplus glutathione-S-transferase (RmGST). RmGST detoxifies acaricides by catalyzing the conjugation of glutathione to acaricides. Although structural and dynamic details of RmGST are expected to elucidate the biologic activity of this molecule, these data have not been available to date. Thus, Molecular Dynamics simulations were employed to study ligand-free RmGST at an atomic level. Like other m-class GSTs, the flexible m loop (m1) of RmGST was observed. M1 seems to shield the active sites from the bulk. A RmGST dimer is stabilized by the lock-and-key motif (F57 as "key") and hydrogen bonds of R82-E91 and R82-D98 at the dimer interface. Without substrates, conserved catalytic Y116 and N209 can interact with V112, G210 (for Y116) and F215 (for N209). Overall, most residues involving in RmGST function and stability are similar to other m-class GSTs. This implies similar structural stability and catalytic activity of RmGST to other GSTs. An insight obtained here will be useful for management of acaricide resistance and tick control.Communicated by Ramaswamy H. Sarma.
Insights
Molecular Dynamics simulations reveal the structure of Rhipicephalus (Boophilus) microplus glutathione-S-transferase (RmGST). This enzyme
Area of Science:
- Veterinary Parasitology
- Molecular Biology
- Biochemistry
Background:
- Rhipicephalus (Boophilus) microplus is a significant cattle parasite globally.
- Rapid acaricide resistance in ticks is a major economic concern for the cattle industry.
- Enhanced metabolic detoxification via R. (B.) microplus glutathione-S-transferase (RmGST) is a key resistance mechanism.
Purpose of the Study:
- To elucidate the atomic-level structural and dynamic details of ligand-free RmGST.
- To understand the molecular basis of RmGST function in acaricide resistance.
- To provide insights for developing strategies against tick resistance.
Main Methods:
- Molecular Dynamics (MD) simulations were performed on ligand-free RmGST.
- Analysis focused on structural features, active site shielding, and dimer interface stability.
- Comparison of RmGST residues with conserved residues in other m-class GSTs.
Main Results:
- The flexible m loop (m1) of RmGST was observed, potentially shielding the active site.
- A stable RmGST dimer is formed via a lock-and-key motif and specific hydrogen bonds.
- Conserved catalytic residues (Y116, N209) interact with other residues in the absence of substrates.
- RmGST shares structural and functional similarities with other m-class GSTs.
Conclusions:
- The study provides the first atomic-level insights into RmGST structure and dynamics.
- Structural similarities suggest comparable stability and catalytic activity to other m-class GSTs.
- Understanding RmGST is crucial for managing acaricide resistance and improving tick control strategies.
