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Thermodynamic analysis of interactions of the Hsp90 with adenosine nucleotides: a comparative perspective.
MINARI, Karine; AZEVEDO, Érika Chang de; KIRALY, Vanessa T. R; BATISTA, Fernanda Aparecida Heleno; MORAES, F. R.; MELO, Fernando Alves de; NASCIMENTO, Alessandro Silva; GAVA, Lisandra Marques; RAMOS, Carlos Henrique Inacio; BORGES, Júlio Cesar.
Abstract: Hsp90s are key proteins in cellular homeostasis since they interact with many client proteins. Several studies indicated that Hsp90s are potential targets for treating diseases, such as cancer or malaria. It has been shown that Hsp90s from different organisms have peculiarities despite their high sequence identity. Therefore, a detailed comparative analysis of several Hsp90 proteins is relevant to the overall understanding of their activity. Accordingly, the goal of this work was to evaluate the interaction of either ADP or ATP with recombinant Hsp90s from different organisms (human a and ß isoforms, Plasmodium falciparum, Leishmania braziliensis, yeast and sugarcane) by isothermal titration calorimetry. The measured thermodynamic signatures of those interactions indicated that despite the high identity among all Hsp90s, they have specific thermodynamic characteristics. Specifically, the interactions with ADP are driven by enthalpy but are opposed by entropy, whereas the interaction with ATP is driven by both enthalpy and entropy. Complimentary structural and molecular dynamics studies suggested that specific interactions with ADP that differ from those with ATP may contribute to the observed enthalpies and entropies. Altogether, the data suggest that selective inhibition may be more easily achieved using analogues of the Hsp90-ADP bound state than those of Hsp90-ATP bound state.
International Journal of Biological Macromolecules
v.130, p.125-138 - Ano: 2019
Fator de Impacto: 3,909
https://doi.org/10.1016/j.ijbiomac.2019.02.116
    @article={002930298,author = {MINARI, Karine; AZEVEDO, Érika Chang de; KIRALY, Vanessa T. R; BATISTA, Fernanda Aparecida Heleno; MORAES, F. R.; MELO, Fernando Alves de; NASCIMENTO, Alessandro Silva; GAVA, Lisandra Marques; RAMOS, Carlos Henrique Inacio; BORGES, Júlio Cesar.},title={Thermodynamic analysis of interactions of the Hsp90 with adenosine nucleotides: a comparative perspective},journal={International Journal of Biological Macromolecules},note={v.130, p.125-138},year={2019}}