Elucidating structure and dynamics of glutathione S-transferase from Rhipicephalus (Boophilus) microplus

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

Keywords:

• Tick
• Glutathione S-transferase
• MD simulation
• Rhipicephalus (Boophilus) microplus

Acknowledgements

We would like to thank Kasetsart University Reinventing University Program 2021 for Post-Doctoral training program and Kasetsart University Research and Development Institute (KURDI) for funding this project (FF(KU) 14.65).

Disclosure statement

No potential conflict of interest was reported by the authors.