ArticleMalaria journal2012
Plasmodium serine hydroxymethyltransferase as a potential anti-malarial target: inhibition studies using improved methods for enzyme production and assay.
Article in Malaria journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- Functional divergence of two soybean cytosolic serine hydroxymethyltransferases in development and defense against soybean cyst nematode.Frontiers in plant science · 2026Article
- Benzilmonoximethiocarbohydrazide Schiff bases as multifunctional antimalarial and antioxidant scaffolds: synthesis, biological evaluation, and mechanistic insights.RSC advances · 2025Article
- A robust strategy for overexpression of DNA polymerase from Thermus aquaticus using an IPTG-independent autoinduction system in a benchtop bioreactor.Scientific reports · 2025Article
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- In Silico and In Vitro Potential of FDA-Approved Drugs for Antimalarial Drug Repurposing againstACS omega · 2023Article
- Characterisation of thePathogens (Basel, Switzerland) · 2022Article
- Characterization of Apicomplexan Amino Acid Transporters (ApiATs) in the Malaria Parasite Plasmodium falciparum.mSphere · 2021Article
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- Amino Acid Metabolism in Apicomplexan Parasites.Metabolites · 2021Review
- Impaired folate binding of serine hydroxymethyltransferase 8 from soybean underlies resistance to the soybean cyst nematode.The Journal of biological chemistry · 2020Article
- Kinetic mechanism and the rate-limiting step of Plasmodium vivax serine hydroxymethyltransferase.The Journal of biological chemistry · 2015Article
- Structures of Plasmodium vivax serine hydroxymethyltransferase: implications for ligand-binding specificity and functional control.Acta crystallographica. Section D, Biological crystallography · 2014Article
- The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Proteome scale comparative modeling for conserved drug and vaccine targets identification in Corynebacterium pseudotuberculosis.BMC genomics · 2014Article
- Plasmodium serine hydroxymethyltransferase: indispensability and display of distinct localization.Malaria journal · 2012Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere is an urgent need for the discovery of new anti-malarial drugs. Thus, it is essential to explore different potential new targets that are unique to the parasite or that are required for its viability in order to develop new interventions for treating the disease. Plasmodium serine hydroxymethyltransferase (SHMT), an enzyme in the dTMP synthesis cycle, is a potential target for such new drugs, but convenient methods for producing and assaying the enzyme are still lacking, hampering the ability to screen inhibitors.
methodsProduction of recombinant Plasmodium falciparum SHMT (PfSHMT) and Plasmodium vivax SHMT (PvSHMT), using auto-induction media, were compared to those using the conventional Luria Bertani medium with isopropyl thio-β-D-galactoside (LB-IPTG) induction media. Plasmodium SHMT activity, kinetic parameters, and response to inhibitors were measured spectrophotometrically by coupling the reaction to that of 5,10-methylenetetrahydrofolate dehydrogenase (MTHFD). The identity of the intermediate formed upon inactivation of Plasmodium SHMTs by thiosemicarbazide was investigated by spectrophotometry, high performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS). The active site environment of Plasmodium SHMT was probed based on changes in the fluorescence emission spectrum upon addition of amino acids and folate.
resultsAuto-induction media resulted in a two to three-fold higher yield of Pf- and PvSHMT (7.38 and 29.29 mg/L) compared to that produced in cells induced in LB-IPTG media. A convenient spectrophotometric activity assay coupling Plasmodium SHMT and MTHFD gave similar kinetic parameters to those previously obtained from the anaerobic assay coupling SHMT and 5,10-methylenetetrahydrofolate reductase (MTHFR); thus demonstrating the validity of the new assay procedure. The improved method was adopted to screen for Plasmodium SHMT inhibitors, of which some were originally designed as inhibitors of malarial dihydrofolate reductase. Plasmodium SHMT was slowly inactivated by thiosemicarbazide and formed a covalent intermediate, PLP-thiosemicarbazone.
conclusionsAuto-induction media offers a cost-effective method for the production of Plasmodium SHMTs and should be applicable for other Plasmodium enzymes. The SHMT-MTHFD coupled assay is equivalent to the SHMT-MTHFR coupled assay, but is more convenient for inhibitor screening and other studies of the enzyme. In addition to inhibitors of malarial SHMT, the development of species-specific, anti-SHMT inhibitors is plausible due to the presence of differential active sites on the Plasmodium enzymes.
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