Analysis of the ATCase catalysis within the amino acid metabolism of the human malaria parasite Plasmodium falciparum

• Grant number: 13/17577-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2014
• End date: March 16, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carsten Wrenger
• Grantee: Soraya Soledad Bosch
• Host 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

The aim of the proposed research project is to evaluate the necessity of the aspartate carbamoyl transferase within the aspartate metabolism of the human malaria parasite Plasmodium falciparum. The respective open reading frame has been identified and will be cloned, and the encoded enzyme recombinantly expressed in order to get conformational and kinetic insights in the catalysis of the plasmodial protein. Mutagenic studies and protein interference experiments will be applied to verify the need of the enzyme for the proliferation of the parasite. As predicted by bioinformatic tools the protein bears an apicoplast-targeting sequence and therefore its localization will be investigated by transfection of green-fluorescent-protein-chimeras. (AU)

Scientific publications

(8)

(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)

LUNEV, SERGEY; BOSCH, SORAYA S.; BATISTA, FERNANDO DE ASSIS; WRENGER, CARSTEN; GROVES, MATTHEW R.. Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 72, n. 7, p. 523-533, JUL 2016. (13/10288-1, 13/17577-9)

BATISTA, FERNANDO A.; BOSCH, SORAYA S.; BUTZLOFF, SABINE; LUNEV, SERGEY; MEISSNER, KAMILA A.; LINZKE, MARLEEN; ROMERO, ATILIO R.; WANG, CHAO; MUELLER, INGRID B.; DOMLING, ALEXANDER S. S.; et al. Oligomeric protein interference validates druggability of aspartate interconversion in Plasmodium falciparum. MICROBIOLOGYOPEN, v. 8, n. 7, JUL 2019. (17/03966-4, 15/26722-8, 16/24790-9, 14/23330-9, 13/17577-9)

BATISTA, FERNANDO A.; GYAU, BENJAMIN; VILACHA, JULIANA F.; BOSCH, SORAYA S.; LUNEV, SERGEY; WRENGER, CARSTEN; GROVES, MATTHEW R.. New directions in antimalarial target validation. EXPERT OPINION ON DRUG DISCOVERY, v. 15, n. 2, p. 189-202, FEB 1 2020. (17/03966-4, 15/26722-8, 13/17577-9)

LUNEV, SERGEY; BOSCH, SORAYA S.; BATISTA, FERNANDO A.; WANG, CHAO; LI, JINGYAO; LINZKE, MARLEEN; KRUITHOF, PAUL; CHAMOUN, GEORGE; DOMLING, ALEXANDER S. S.; WRENGER, CARSTEN; et al. Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase. Biochemical and Biophysical Research Communications, v. 497, n. 3, p. 835-842, MAR 11 2018. (15/26722-8, 13/17577-9, 14/23330-9)

BOSCH, SORAYA S.; LUNEV, SERGEY; BATISTA, FERNANDO A.; LINZKE, MARLEEN; KRONENBERGER, THALES; DOMLING, ALEXANDER S. S.; GROVES, MATTHEW R.; WRENGER, CARSTEN. Molecular Target Validation of Aspartate Transcarbamoylase from Plasmodium falciparum by Torin 2. ACS INFECTIOUS DISEASES, v. 6, n. 5, p. 986-999, MAY 8 2020. (17/03966-4, 15/26722-8, 13/17577-9, 14/23330-9)

LUNEV, SERGEY; BOSCH, SORAYA S.; BATISTA, FERNANDO DE ASSIS; WRENGER, CARSTEN; GROVES, MATTHEW R.. Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 72, p. 11-pg., 2016-07-01. (13/10288-1, 13/17577-9)

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. (11/19703-6, 12/12807-3, 11/13706-3, 09/54325-2, 10/20647-0, 13/10288-1, 13/17577-9)

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, v. 2015, p. 10-pg., 2015-01-01. (13/10288-1, 10/20647-0, 09/54325-2, 11/13706-3, 13/17577-9, 12/12807-3, 11/19703-6)

Academic Publications

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

BOSCH, Soraya Soledad. Analysis of the ATCase catalysis within the amino acid metabolism of the human malaria parasite Plasmodium falciparum .. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.