
Model and simulation of Na+/K+ pump phosphorylation in the presence of palytoxin
2007; Elsevier BV; Volume: 32; Issue: 1 Linguagem: Inglês
10.1016/j.compbiolchem.2007.08.001
ISSN1476-928X
AutoresAntônio Márcio Rodrigues, Antônio-Carlos G. de Almeida, A. F. C. Infantosi, Hewerson Z. Teixeira, Mário Antônio Duarte,
Tópico(s)Magnesium in Health and Disease
ResumoThe ATP hydrolysis reactions responsible for the Na+/K+-ATPase phosphorylation, according to recent experimental evidences, also occur for the PTX–Na+/K+ pump complex. Moreover, it has been demonstrated that PTX interferes with the enzymes phosphorylation status. However, the reactions involved in the PTX–Na+/K+ pump complex phosphorylation are not very well established yet. This work aims at proposing a reaction model for PTX–Na+/K+ pump complex, with similar structure to the Albers–Post model, to contribute to elucidate the PTX effect over Na+/K+-ATPase phosphorylation and dephosphorylation. Computational simulations with the proposed model support several hypotheses and also suggest: (i) phosphorylation promotes an increase of the open probability of induced channels; (ii) PTX reduces the Na+/K+ pump phosphorylation rate; (iii) PTX may cause conformational changes to substates where the Na+/K+-ATPase may not be phosphorylated; (iv) PTX can bind to substates of the two principal states E1 and E2, with highest affinity to phosphorylated enzymes and with ATP bound to its low-affinity sites. The proposed model also allows previewing the behavior of the PTX–pump complex substates for different levels of intracellular ATP concentrations.
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