Binding of green tea epigallocatechin gallate to the arginine kinase active site from the brown recluse spider (Loxosceles laeta): A potential synergist to chemical pesticides
Por:
Moreno-Cordova E.N., Alvarez-Armenta A., Garcia-Orozco K.D., Arvizu-Flores A.A., Islas-Osuna M.A., Robles-Zepeda R.E., Lopez-Zavala A.A., Laino A., Sotelo-Mundo R.R.
Publicada:
1 ene 2024
Categoría:
Multidisciplinary
Resumen:
Loxosceles spp. spiders can cause serious public health issues. Chemical control is commonly used, leading to health and environmental problems. Identifying molecular targets and using them with natural compounds can help develop safer and eco-friendlier biopesticides. We studied the kinetics and predicted structural characteristics of arginine kinase (EC 2.7.3.3) from Loxosceles laeta (LlAK), a key enzyme in the energy metabolism of these organisms. Additionally, we explored (-)-epigallocatechin gallate (EGCG), a green tea flavonoid, as a potential lead compound for the LlAK active site through fluorescence and in silico analysis, such as molecular docking and molecular dynamics (MD) simulation and MM/PBSA analyses. The results indicate that LlAK is a highly efficient enzyme (KmArg 0.14 mM, KmATP 0.98 mM, kcat 93 s-1, kcat/KmArg 630 s-1 mM-1, kcat/KmATP 94 s-1 mM-1), which correlates with its structure similarity to others AKs (such as Litopenaeus vannamei, Polybetes pythagoricus, and Rhipicephalus sanguineus) and might be related to its important function in the spider's energetic metabolism. Furthermore, the MD and MM/PBSA analysis suggests that EGCG interacted with LlAK, specifically at ATP/ADP binding site (RMSD <1 nm) and its interaction is energetically favored for its binding stability (-40 to -15 kcal/mol). Moreover, these results are supported by fluorescence quenching analysis (Kd 58.3 µM and Ka 1.71 × 104 M-1). In this context, LlAK is a promising target for the chemical control of L. laeta, and EGCG could be used in combination with conventional pesticides to manage the population of Loxosceles species in urban areas. © 2024 The Authors
Filiaciones:
Laboratorio de Estructura Biomolecular, Centro de Investigación en Alimentación y Desarrollo, A. C., Sonora, Hermosillo, Mexico
Departamento de Microbiologia Molecular, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Avenida Universidad 2001, Morelos, Cuernavaca, 62210, Mexico
Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Sonora, Hermosillo, Mexico
Laboratorio de Biología Molecular de Plantas, Centro de Investigación en Alimentación y Desarrollo, A. C., Sonora, Hermosillo, Mexico
Instituto de Investigaciones Bioquímicas de La Plata “Prof. Dr. Rodolfo R. Brenner” (INIBIOLP), Centro Científico Tecnológico – La Plata CONICET- Univerdad Nacional de La Plata, La Plata, Argentina
gold, All Open Access; Gold Open Access
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