Calcium-calmodulin of Plasmodium falciparum: identification of ligands and participation in the host-parasite signalling

• Grant number: 13/12913-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2014
• Effective date (End): November 30, 2016
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Adriana Karaoglanovic Carmona
• Grantee: Alexandre Budu
• Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil

Abstract

Calcium as a second-messenger is essential for Plasmodium falciparum. Many aspects of intracellular signaling are unknown in the parasite, however some of the calcium effectors, as calmodulin, are annotated in the genome of Plasmodium. Calmodulin is an enzyme present in all eukaryotes and may be responsible for the activation of kinases, ionic channels and regulation of calcium homeostasis. The in silico prediction of the domains which bind calmodulin is seldom precise, due to the variability of these regions. The objectives of the project are to identify enzymes activated by calmodulin in Plasmodium. We will characterize the participation of calmodulin in the calcium homeostasis and proteolitic activity of the parasite, as well as the role of calmodulin in the generation of bioactive peptides that act as extracellular signals for the host.

Scientific publications

(5)

(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)

GOMES SMAUL, MAYRIM MACHADO; BUDU, ALEXANDRE; MONTAGNA, GEORGINA NURI; DA SILVA FERRARA, TAISE FERNANDA; MALUF, SARAH EL CHAMY; BAGNARESI, PIERO; FERREIRA MACHADO, MARCELO MARCONDES; DOS SANTOS, FELLIPE BRONZE; DE AZEVEDO, MAURO FERREIRA; CARMONA, ADRIANA KARAOGLANOVIC; GAZARINI, MARCOS LEONI. Plasmodium falciparum histidine triad protein and calmodulin modulates calcium homeostasis and intracellular proteolysis. Biochemical and Biophysical Research Communications, v. 503, n. 2, p. 722-728, SEP 5 2018. Web of Science Citations: 0.

MELO, POLLYANA M. S.; MALUF, SARAH EL CHAMY; AZEVEDO, MAURO F.; PASCHOALIN, THAYSA; BUDU, ALEXANDRE; BAGNARESI, PIERO; HENRIQUE-SILVA, FLAVIO; SOARES-COSTA, ANDREA; GAZARINI, MARCOS L.; CARMONA, ADRIANA K. Inhibition of Plasmodium falciparum cysteine proteases by the sugarcane cystatin CaneCPI-4. Parasitology International, v. 67, n. 2, p. 233-236, APR 2018. Web of Science Citations: 6.

GONZALEZ-BACERIO, JORGE; MALUF, SARAH EL CHAMY; MENDEZ, YANIRA; PASCUAL, ISEL; FLORENT, ISABELLE; MELO, POLLYANA M. S.; BUDU, ALEXANDRE; FERREIRA, JULIANA C.; MORENO, ERNESTO; CARMONA, ADRIANA K.; RIVERA, DANIEL G.; DEL RIVERO, MADAY ALONSO; GAZARINI, MARCOS L. KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library. Bioorganic & Medicinal Chemistry, v. 25, n. 17, p. 4628-4636, SEP 1 2017. Web of Science Citations: 2.

BUDU, ALEXANDRE; GOMES, MAYRIM M.; MELO, POLLYANA M.; MALUF, SARAH EL CHAMY; BAGNARESI, PIERO; AZEVEDO, MAURO F.; CARMONA, ADRIANA K.; GAZARINI, MARCOS L. Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum. CELLULAR SIGNALLING, v. 28, n. 3, p. 125-135, MAR 2016. Web of Science Citations: 2.

GOMES, MAYRIM M.; BUDU, ALEXANDRE; VENTURA, PRISCILLA D. S.; BAGNARESI, PIERO; COTRIN, SIMONE S.; CUNHA, RODRIGO L. O. R.; CARMONA, ADRIANA K.; JULIANO, LUIZ; GAZARINI, MARCOS L. Specific calpain activity evaluation in Plasmodium parasites. Analytical Biochemistry, v. 468, p. 22-27, JAN 1 2015. Web of Science Citations: 5.