Implications from pyridoxine kinase of Plasmodium falciparum and study if its spacer regions

• Grant number: 11/13706-3
• Support type: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): December 31, 2013
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Carsten Wrenger
• Grantee: Thales Kronenberger
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/54325-2 - Elucidation of vitamin B metabolism in the human malaria parasite Plasmodium falciparum and their validation as a target for chemotherapy, AP.JP

Abstract

Malaria is a disease caused by a parasite that has a complex life cycle, with one of its phases occurring in humans. The parasite attacks directly the main organs, e.g. the liver, by the means of cell proliferation cycles, that may cause a great number of synptoms in other organs, as the brain or the lungs. One of the worst types of the disease in humans is caused by the specie Plasmodium falciparum being responsible by a significant parcel from the 247 million cases of malaria. Nowadays it is fought by the use of drugs, for example, the Artemisin. However this use has showed increased inefficiency due to the spreading of the resistance to antibiotics among the parasite population, in part related to a beforehand interrupted treatment. As there isnt yet an effective vaccine against malaria, one strategy to control it, besides those related to the vector, would be the search for new drugs, a process that uses the combined knowledge from the parasite's metabolic pathway with its protein structures, among other areas. According to these propositions the study of the PdxK protein and its spacers regions (found only on homologs of the genre Plasmodium) shows candidates for drug targets, as this enzyme is related in the conversion of B6 vitamers to its phosphorilated form (PLP), that is an essencial cofactor for many enzymatic reactions and is therefore important for many of the parasite's pathways. (AU)

Scientific publications

(4)

(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)

BOSCH, SORAYA S.; KRONENBERGER, THALES; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; STEGEHAKE, DIRK; IZUI, NATALIA M.; SCHETTERT, ISOLMAR; LIEBAU, EVA; WRENGER, CARSTEN. Oxidative Stress Control by Apicomplexan Parasites. BIOMED RESEARCH INTERNATIONAL, 2015. Web of Science Citations: 10.

KRONENBERGER, THALES; LUNEV, SERGEY; WRENGER, CARSTEN; GROVES, MATTHEW R. Purification, crystallization and preliminary X-ray diffraction analysis of pyridoxal kinase from Plasmodium falciparum (PfPdxK). ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 70, n. 11, p. 1550-1555, NOV 2014. Web of Science Citations: 0.

KRONENBERGER, THALES; LINDNER, JASMIN; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; CORONADO, MONIKA A.; SAUER, FRANK M.; SCHETTERT, ISOLMAR; WRENGER, CARSTEN. Vitamin B6-Dependent Enzymes in the Human Malaria Parasite Plasmodium falciparum: A Druggable Target?. BIOMED RESEARCH INTERNATIONAL, 2014. Web of Science Citations: 9.

KRONENBERGER, THALES; SCHETTERT, ISOLMAR; WRENGER, CARSTEN. Targeting the vitamin biosynthesis pathways for the treatment of malaria. Future Medicinal Chemistry, v. 5, n. 7, p. 769-779, MAY 2013. Web of Science Citations: 4.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

KRONENBERGER, Thales. Structural implication of mutans of the pyridoxal kinase from Plasmodium falciparum.. 2014. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas São Paulo.