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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Thermodynamic analysis of interactions of the Hsp90 with adenosine nucleotides: A comparative perspective

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Author(s):
Minari, Karine [1, 2] ; de Azevedo, Erika Chang [3] ; Rodrigues Kiraly, Vanessa Thomaz [1] ; Heleno Batista, Fernanda Aparecida [1] ; de Moraes, Fabio Rogerio [4] ; de Melo, Fernando Alves [4] ; Nascimento, Alessandro Silva [3] ; Gava, Lisandra Marques [2] ; Inacio Ramos, Carlos Henrique [5] ; Borges, Julio Cesar [1]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Sao Carlos Inst Chem, BR-13566590 Sao Carlos, SP - Brazil
[2] Univ Fed Sao Carlos, Ctr Biol & Hlth Sci, BR-13560970 Sao Carlos, SP - Brazil
[3] Univ Sao Paulo, Sao Carlos Inst Phys, BR-13560970 Sao Carlos, SP - Brazil
[4] Sao Paulo State Univ, Multiuser Ctr Biol Innovat CMIB, Biosci Languages & Exact Sci Inst, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[5] Univ Campinas UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: International Journal of Biological Macromolecules; v. 130, p. 125-138, JUN 1 2019.
Web of Science Citations: 1
Abstract

Hsp90s are key proteins in cellular homeostasis since they interact with many client proteins. Several studies indicated that Hsp9Os are potential targets for treating diseases, such as cancer or malaria. It has been shown that Hsp9Os 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 Hsp9Os from different organisms ( human et and (3 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. (C) 2019 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
Grantee:Carsten Wrenger
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/25646-0 - Comparative functional studies of Hsp90 from different organisms
Grantee:Karine Minari
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 17/18173-0 - Mechanisms Involved in Resistance to Antibiotics: Wall Teichoic Acids and Biofilms as Molecular Targets
Grantee:Alessandro Silva Nascimento
Support Opportunities: Regular Research Grants
FAPESP's process: 11/23110-0 - Using isothermal titration calorimetry for the determination of thermodynamic properties of protein-ligand and protein-protein interactions
Grantee:Julio Cesar Borges
Support Opportunities: Regular Research Grants
FAPESP's process: 14/07206-6 - Studies of the mitochondrial HSP70 of human and protozoa: structural and functional approaches
Grantee:Julio Cesar Borges
Support Opportunities: Regular Research Grants
FAPESP's process: 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis
Grantee:Carlos Henrique Inacio Ramos
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules
Grantee:Raghuvir Krishnaswamy Arni
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 17/07335-9 - Studies of human HSP70 isoforms residing in the cytoplasm and mitochondria and their high molecular weight oligomers: interaction with co-chaperones and client proteins
Grantee:Julio Cesar Borges
Support Opportunities: Regular Research Grants