Comparative functional studies of Hsp90 from different organisms

• Grant number: 13/25646-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2014
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Julio Cesar Borges
• Grantee: Karine Minari
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis, AP.TEM

Abstract

Hsp90 (Heat shock protein 90 kDa) is found in all organisms and in all cellular compartments, interacting with at least 10% of all proteins produced by the cell. Hsp90 plays essential roles in the maturation of these proteins, making it an important protein for diverse cellular processes such that signaling Proteostasis, epigenetics, telomere maintenance, innate immunity and others. More than 200 client proteins of Hsp90 have been described and they can be classified into three groups: corticoid hormone receptors, protein kinases and unrelated proteins. The function of Hsp90 is headed by dynamic association with client proteins and co-chaperones, which form complexes with other cellular proteins and molecular chaperones. Currently, inhibitors of Hsp90 (as geldanamycin, radicicol and 17-GGA) have been suggested as potential drug prototypes for the treatment of some types of cancer and there are studies that suggest the potential of developing selective inhibitors of Hsp90 protozoa as Plasmodium falciparum, Leishmania donovani, Trypanosoma cruzi and Leishmania amazonensis. Hsp90 have similar functions in different organisms, however they present mechanistic peculiarities, differences in ATPase activity, interaction with ligands and proteins clients and post-translational modifications. The aim of this PhD project is to evaluate some of the functional properties of Hsp90 some organisms (human, yeast, Leishmania braziliensis, P. falciparum, oranges and sugarcane) using the same methodologies to allow broad comparative functional characterization. Allowing thus outcome parameters set of Hsp90 and to evaluate the effects of the first generation inhibitors of Hsp90 as geldanamycin, radicicol and 17-GGA. Prospect new ligands/inhibitors of Hsp90 from a set of marine compounds is also objective of this project. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MINARI, KARINE; DE AZEVEDO, ERIKA CHANG; RODRIGUES KIRALY, VANESSA THOMAZ; HELENO BATISTA, FERNANDA APARECIDA; DE MORAES, FABIO ROGERIO; DE MELO, FERNANDO ALVES; NASCIMENTO, ALESSANDRO SILVA; GAVA, LISANDRA MARQUES; INACIO RAMOS, CARLOS HENRIQUE; BORGES, JULIO CESAR. Thermodynamic analysis of interactions of the Hsp90 with adenosine nucleotides: A comparative perspective. International Journal of Biological Macromolecules, v. 130, p. 125-138, JUN 1 2019. (15/26722-8, 13/25646-0, 17/18173-0, 11/23110-0, 14/07206-6, 12/50161-8, 09/53989-4, 17/07335-9)

SILVA, NOELI S. M.; SERAPHIM, THIAGO V.; MINARI, KARINE; BARBOSA, LEANDRO R. S.; BORGES, JULIO C.. Comparative studies of the low-resolution structure of two p23 co-chaperones for Hsp90 identified in Plasmodium falciparum genome. International Journal of Biological Macromolecules, v. 108, p. 193-204, MAR 2018. (14/07206-6, 13/25646-0, 11/23110-0, 12/50161-8, 12/01953-9, 17/07335-9, 15/15822-1)