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Binding of the plant-derived toxin simplexin to bovine protein kinase C: insights from molecular dynamics

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Zhou, Y., Roseli, R. B., Hungerford, N. L., Fletcher, M. T., Ouwerkerk, D., Gilbert, R. A. and Krenske, E. H. (2024) Binding of the plant-derived toxin simplexin to bovine protein kinase C: insights from molecular dynamics. Organic & Biomolecular Chemistry, 22 (14). pp. 2863-2876. ISSN 1477-0520

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Article Link: http://dx.doi.org/10.1039/D4OB00065J


Pimelea poisoning of cattle is toxicologically linked to the activation of bovine protein kinase C (PKC) by the plant-derived toxin simplexin. To understand the affinity of PKC for simplexin, we performed molecular dynamics (MD) studies of simplexin, simplexin analogues, and several other activators of PKC. Binding enthalpy calculations indicated that simplexin had the strongest affinity for PKCα-C1B among the activators studied. Key to simplexin's affinity is its ability to form more hydrogen bonds to PKC, compared to the other activators. The C-3 carbonyl group and C-20 hydroxyl group of simplexin were identified as especially important for stabilizing the PKC binding interaction. The hydrophobic alkyl chain of simplexin induces deep membrane embedding of the PKC–simplexin complex, enhancing the protein–ligand hydrogen bonding. Our findings align with previous experiments on structure–activity relationships (SAR) for simplexin analogues, and provide insights that may guide the development of interventions or treatments for Pimelea poisoning.

Item Type:Article
Corporate Creators:Department of Agriculture and Fisheries, Queensland
Business groups:Animal Science
Subjects:Science > Microbiology > Microorganisms in the animal body
Agriculture > Agriculture (General) > Agricultural chemistry. Agricultural chemicals
Animal culture > Cattle
Live Archive:08 Apr 2024 05:56
Last Modified:08 Apr 2024 05:56

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