GTP is an allosteric modulator of the interaction between the guanylate-binding protein 1 and the prosurvival kinase PIM1

•Binding of GBP1 to the prosurvival kinase PIM1 induces resistance to paclitaxel.•Molecular simulations indicated that GTP hydrolysis affects GBP1:PIM1 interaction through an allosteric mechanism.•Experimental data confirmed that GTP decrease the formation of the GBP1:PIM1 complex in a dose-dependent manner.•GDP has no effect on the GBP1:PIM1 interaction.•A new approach for the design of therapeutics capable to revert paclitaxel resistance.

GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel.

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