Abstract
The carmine spider mite, Tetranychus cinnabarinus (Boisduval), is an economically important agricultural pest that is difficult to prevent and control. Scopoletin is a botanical coumarin derivative that targets Ca2+-ATPase to exert a strong acaricidal effect on carmine spider mites. In this study, the full-length cDNA sequence of a plasma membrane Ca2+-ATPase 1 gene (TcPMCA1) was cloned. The sequence contains an open reading frame of 3750 bp and encodes a putative protein of 1249 amino acids. The effects of scopoletin on TcPMCA1 expression were investigated. TcPMCA1 was significantly upregulated after it was exposed to 10%, 30%, and 50% of the lethal concentration of scopoletin. Homology modeling, molecular docking, and three-dimensional quantitative structure-activity relationships were then studied to explore the relationship between scopoletin structure and TcPMCA1-inhibiting activity of scopoletin and other 30 coumarin derivatives. Results showed that scopoletin inserts into the binding cavity and interacts with amino acid residues at the binding site of the TcPMCA1 protein through the driving forces of hydrogen bonds. Furthermore, CoMFA (comparative molecular field analysis)- and CoMSIA (comparative molecular similarity index analysis)-derived models showed that the steric and H-bond fields of these compounds exert important influences on the activities of the coumarin compounds.Notably, the C3, C6, and C7 positions in the skeletal structure of the coumarins are the most suitable active sites. This work provides insights into the mechanism underlying the interaction of scopoletin with TcPMCA1. The present results can improve the understanding on plasma membrane Ca2+-ATPase-mediated (PMCA-mediated) detoxification of scopoletin and coumarin derivatives in T. cinnabarinus, as well as provide valuable information for the design of novel PMCA-inhibiting acaricides.
Highlights
The plasma membrane Ca2+-ATPase (PMCA) pumps Ca2+ out of the cell to maintain cytosolic Ca2+ concentration at a level that is compatible with messenger function
The remaining 5 and 3 ends were amplified through a rapid amplification of cDNA ends (RACE)/PCR (Polymerase Chain Reaction)-based strategy
These results revealed that scopoletin inserts into the binding cavity and interacts with the active sites of TcPMCA1, suggesting that the microenvironments and conformation of the enzymes change because of these interactions [47]
Summary
The plasma membrane Ca2+-ATPase (PMCA) pumps Ca2+ out of the cell to maintain cytosolic Ca2+ concentration at a level that is compatible with messenger function. PMCAs exhibit cell-specific expression patterns and play an essential role in Ca2+ homeostasis in various cell types, including sensory neurons [4,5,6,7]. Human PMCA1 is shown to be more abundant than PMCA4 at mRNA and protein levels [11]. Numerous methods, such as transient transfection, the use of stable cell lines, and use of the vaccinia viral vector, are used to advance knowledge on the differential properties of these isoforms [12,13,14]
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