scholarly journals Use of Radioactive Precursors for Biochemical Characterization the Biosynthesis of Isoprenoids in Intraerythrocytic Stages of Plasmodium falciparum

Author(s):  
Emilia A. ◽  
Gerhard Wunderlich ◽  
Fabiana M. ◽  
Renata Tonhosolo ◽  
Heloisa B. ◽  
...  
2013 ◽  
Vol 450 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Sweta Maheshwari ◽  
Marina Lavigne ◽  
Alicia Contet ◽  
Blandine Alberge ◽  
Emilie Pihan ◽  
...  

The intra-erythrocytic proliferation of the human malaria parasite Plasmodium falciparum requires massive synthesis of PE (phosphatidylethanolamine) that together with phosphatidylcholine constitute the bulk of the malaria membrane lipids. PE is mainly synthesized de novo by the CDP:ethanolamine-dependent Kennedy pathway. We previously showed that inhibition of PE biosynthesis led to parasite death. In the present study we characterized PfECT [P. falciparum CTP:phosphoethanolamine CT (cytidylyltransferase)], which we identified as the rate-limiting step of the PE metabolic pathway in the parasite. The cellular localization and expression of PfECT along the parasite life cycle were studied using polyclonal antibodies. Biochemical analyses showed that the enzyme activity follows Michaelis–Menten kinetics. PfECT is composed of two CT domains separated by a linker region. Activity assays on recombinant enzymes upon site-directed mutagenesis revealed that the N-terminal CT domain was the only catalytically active domain of PfECT. Concordantly, three-dimensional homology modelling of PfECT showed critical amino acid differences between the substrate-binding sites of the two CT domains. PfECT was predicted to fold as an intramolecular dimer suggesting that the inactive C-terminal domain is important for dimer stabilization. Given the absence of PE synthesis in red blood cells, PfECT represents a potential antimalarial target opening the way for a rational conception of bioactive compounds.


2006 ◽  
Vol 61 (4) ◽  
pp. 948-959 ◽  
Author(s):  
Ian W. Boucher ◽  
Paul J. McMillan ◽  
Mads Gabrielsen ◽  
Susan E. Akerman ◽  
James A. Brannigan ◽  
...  

2018 ◽  
Vol 86 (11) ◽  
pp. 1189-1201 ◽  
Author(s):  
Blessing Mabate ◽  
Tawanda Zininga ◽  
Lebogang Ramatsui ◽  
Stanley Makumire ◽  
Ikechukwu Achilonu ◽  
...  

2011 ◽  
Vol 175 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Flora Wang ◽  
Priscilla Krai ◽  
Edgar Deu ◽  
Brittney Bibb ◽  
Conni Lauritzen ◽  
...  

FEBS Open Bio ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1909-1927
Author(s):  
Manish Chauhan ◽  
Suman Sourabh ◽  
Rahena Yasmin ◽  
Isha Pahuja ◽  
Renu Tuteja

1990 ◽  
Vol 43 (6) ◽  
pp. 584-596 ◽  
Author(s):  
Peter Goldie ◽  
Eugene F. Roth ◽  
Jerome P. Vanderberg ◽  
Joel Oppenheim

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