AI Article Synopsis
- The protozoan parasite Plasmodium falciparum, responsible for severe malaria, relies heavily on glycolysis for energy production.
- Researchers focused on specific cysteine residues in the pyruvate kinase enzyme (PfPK), finding that mutations at positions C49 and C343 negatively impacted the enzyme's structure and function.
- The mutation of C49 resulted in significant conformational changes and reduced substrate binding, leading to impaired catalytic activity, showing how critical these residues are for maintaining enzyme efficiency.
Article Abstract
The protozoan parasite Plasmodium falciparum causes the most severe form of malaria and is highly dependent on glycolysis. Glycolytic enzymes were shown to be massively redox regulated, inter alia via oxidative post-translational modifications (oxPTMs) of their cysteine residues. In this study, we identified P. falciparum pyruvate kinase (PfPK) C49 and C343 as amino acid residues essentially involved in maintaining structural and functional integrity of the enzyme. The mutation of these cysteines resulted in an altered substrate affinity, lower enzymatic activities, and, as studied by X-ray crystallography, conformational changes within the A-domain where the substrate binding site is located. Although the loss of a cysteine evoked an impaired catalysis in both mutants, the effects observed for mutant C49A were more severe: multiple conformational changes, caused by the loss of two hydrogen bonds, impeded proper substrate binding and thus the transfer of phosphate upon catalysis.
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| http://dx.doi.org/10.1016/j.str.2022.08.001 | DOI Listing |
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