Zobrazit v EDS

Distinct evolution of type I glutamine synthetase in Plasmodium and its species-specific requirement.

Uloženo v:
Podrobná bibliografie
Název: Distinct evolution of type I glutamine synthetase in Plasmodium and its species-specific requirement.
Autoři: Ghosh, Sourav, Kundu, Rajib, Chandana, Manjunatha, Das, Rahul, Anand, Aditya, Beura, Subhashree, Bobde, Ruchir Chandrakant, Jain, Vishal, Prabhu, Sowmya Ramakant, Behera, Prativa Kumari, Mohanty, Akshaya Kumar, Chakrapani, Mahabala, Satyamoorthy, Kapaettu, Suryawanshi, Amol Ratnakar, Dixit, Anshuman, Padmanaban, Govindarajan, Nagaraj, Viswanathan Arun
Zdroj: Nature Communications; 7/14/2023, Vol. 14 Issue 1, p1-27, 27p
Témata: GLUTAMINE synthetase, PLASMODIUM, LIFE cycles (Biology), PLASMODIUM falciparum, AMINO acids, GLUFOSINATE
Abstrakt: Malaria parasite lacks canonical pathways for amino acid biosynthesis and depends primarily on hemoglobin degradation and extracellular resources for amino acids. Interestingly, a putative gene for glutamine synthetase (GS) is retained despite glutamine being an abundant amino acid in human and mosquito hosts. Here we show Plasmodium GS has evolved as a unique type I enzyme with distinct structural and regulatory properties to adapt to the asexual niche. Methionine sulfoximine (MSO) and phosphinothricin (PPT) inhibit parasite GS activity. GS is localized to the parasite cytosol and abundantly expressed in all the life cycle stages. Parasite GS displays species-specific requirement in Plasmodium falciparum (Pf) having asparagine-rich proteome. Targeting PfGS affects asparagine levels and inhibits protein synthesis through eIF2α phosphorylation leading to parasite death. Exposure of artemisinin-resistant Pf parasites to MSO and PPT inhibits the emergence of viable parasites upon artemisinin treatment. In a study looking to examine the functional significance of glutamine synthetase (GS), the authors show that in Plasmodium, GS has evolved as a distinct type I enzyme with unique biochemical and structural features that complement the parasite niche. [ABSTRACT FROM AUTHOR]
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Databáze: Complementary Index
Popis
Abstrakt:Malaria parasite lacks canonical pathways for amino acid biosynthesis and depends primarily on hemoglobin degradation and extracellular resources for amino acids. Interestingly, a putative gene for glutamine synthetase (GS) is retained despite glutamine being an abundant amino acid in human and mosquito hosts. Here we show Plasmodium GS has evolved as a unique type I enzyme with distinct structural and regulatory properties to adapt to the asexual niche. Methionine sulfoximine (MSO) and phosphinothricin (PPT) inhibit parasite GS activity. GS is localized to the parasite cytosol and abundantly expressed in all the life cycle stages. Parasite GS displays species-specific requirement in Plasmodium falciparum (Pf) having asparagine-rich proteome. Targeting PfGS affects asparagine levels and inhibits protein synthesis through eIF2α phosphorylation leading to parasite death. Exposure of artemisinin-resistant Pf parasites to MSO and PPT inhibits the emergence of viable parasites upon artemisinin treatment. In a study looking to examine the functional significance of glutamine synthetase (GS), the authors show that in Plasmodium, GS has evolved as a distinct type I enzyme with unique biochemical and structural features that complement the parasite niche. [ABSTRACT FROM AUTHOR]
ISSN:20411723
DOI:10.1038/s41467-023-39670-4