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Biochemical and physiological investigations on adenosine 5' monophosphate deaminase from Plasmodium spp.
- Source :
-
Molecular microbiology [Mol Microbiol] 2019 Aug; Vol. 112 (2), pp. 699-717. Date of Electronic Publication: 2019 Jul 05. - Publication Year :
- 2019
-
Abstract
- The interplay between ATP generating and utilizing pathways in a cell is responsible for maintaining cellular ATP/energy homeostasis that is reflected by Adenylate Energy Charge (AEC) ratio. Adenylate kinase (AK), that catalyzes inter-conversion of ADP, ATP and AMP, plays a major role in maintaining AEC and is regulated by cellular AMP levels. Hence, the enzymes AMP deaminase (AMPD) and nucleotidases, which catabolize AMP, indirectly regulate AK activity and in-turn affect AEC. Here, we present the first report on AMPD from Plasmodium, the causative agent of malaria. The recombinant enzyme expressed in Saccharomyces cerevisiae was studied using functional complementation assay and residues vital for enzyme activity have been identified. Similarities and differences between Plasmodium falciparum AMPD (PfAMPD) and its homologs from yeast, Arabidopsis and humans are also discussed. The AMPD gene was deleted in the murine malaria parasite P. berghei and was found to be dispensable during all stages of the parasite life cycle. However, when episomal expression was attempted, viable parasites were not obtained, suggesting that perturbing AMP homeostasis by over-expressing AMPD might be lethal. As AMPD is known to be allosterically modulated by ATP, GTP and phosphate, allosteric activators of PfAMPD could be developed as anti-parasitic agents.<br /> (© 2019 John Wiley & Sons Ltd.)
- Subjects :
- AMP Deaminase genetics
Adenosine Monophosphate metabolism
Adenosine Triphosphate metabolism
Allosteric Regulation
Animals
Catalysis
Humans
Malaria, Falciparum parasitology
Mice
Mice, Inbred C57BL
Plasmodium falciparum chemistry
Plasmodium falciparum genetics
Plasmodium falciparum growth & development
Protozoan Proteins genetics
AMP Deaminase chemistry
AMP Deaminase metabolism
Plasmodium falciparum enzymology
Protozoan Proteins chemistry
Protozoan Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2958
- Volume :
- 112
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 31132185
- Full Text :
- https://doi.org/10.1111/mmi.14313