Characterization and redox regulation of Plasmodium falciparum methionine adenosyltransferase
| Autor: | Katja Becker, Jette Pretzel, Karin Fritz-Wolf, Esther Jortzik, Marina Gehr, Stefan Rahlfs, Maike Eisenkolb, Lihui Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine chemistry.chemical_classification Plasmodium falciparum Mutation Missense Protozoan Proteins Methionine Adenosyltransferase General Medicine S-Nitrosylation Methylation Biochemistry Redox 03 medical and health sciences 030104 developmental biology Enzyme Amino Acid Substitution chemistry Mutagenesis Site-Directed Thioredoxin S-Glutathionylation Oxidation-Reduction Molecular Biology Cysteine |
| Zdroj: | The Journal of Biochemistry |
| Popis: | 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 (PfalMAT). Notably, however, PfalMAT 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 PfalMAT. 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 PfalMAT by influencing its structure and activity. This phenomenon connects cellular S-adenosylmethionine synthesis to the redox state of PfalMAT and therefore to the cellular redox homeostasis. |
| Databáze: | OpenAIRE |
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