Journal article

Publication year: 2016

Pages: 355-367

Journal: The Journal of Biochemistry

Volume number: 160

Issue number: 6

ISSN: 0021-924X

eISSN: 1756-2651

DOI Link: https://doi.org/10.1093/jb/mvw045

Publisher: Oxford University Press

Abstract: 
As a methyl group donor for biochemical reactions, S-adenosylmethionine plays a central metabolic role in most organisms. Depletion of S-adenosylmethionine has downstream effects on polyamine metabolism and methylation reactions, and is an effective way to combat pathogenic microorganisms such as malaria parasites. Inhibition of both the methylation cycle and polyamine synthesis strongly affects Plasmodium falciparum growth. Despite its central position in the methylation cycle, not much is currently known about P. falciparum methionine adenosyltransferase (PfaIMAT). Notably, however, Pfa1MAT has been discussed as a target of different redox regulatory modifications. Modulating the redox state of critical cysteine residues is a way to regulate enzyme activity in different pathways in response to changes in the cellular redox state. In the present study, we optimized an assay for detailed characterization of enzymatic activity and redox regulation of Pfa1MAT. While the presence of reduced thioredoxin increases the activity of the enzyme, it was found to be inhibited upon S-glutathionylation. and S-nitrosylation. A homology model and site-directed mutagenesis studies revealed a contribution of the residues Cys52, Cys113 and Cys187 to redox regulation of PfaIMAT by influencing its structure and activity. This phenomenon connects cellular S-adenosylmethionine synthesis to the redox state of PfaIMAT and therefore to the cellular redox homeostasis.

Harvard Citation style: Pretzel, J., Gehr, M., Eisenkolb, M., Wang, L., Fritz-Wolf, K., Rahlfs, S., et al. (2016) Characterization and redox regulation of Plasmodium falciparum methionine adenosyltransferase, The Journal of Biochemistry, 160(6), pp. 355-367. https://doi.org/10.1093/jb/mvw045

APA Citation style: Pretzel, J., Gehr, M., Eisenkolb, M., Wang, L., Fritz-Wolf, K., Rahlfs, S., Becker, K., & Jortzik, E. (2016). Characterization and redox regulation of Plasmodium falciparum methionine adenosyltransferase. The Journal of Biochemistry. 160(6), 355-367. https://doi.org/10.1093/jb/mvw045