Thiamine pyrophosphate (TPP), the active form of vitamin B1, is an essential cofactor for several enzymes. Humans depend exclusively on the uptake of vitamin B1, whereas bacteria, plants, fungi and the malaria parasite Plasmodium falciparum are able to synthesise thiamine monophosphate (TMP) de novo. TMP has to be dephosphorylated prior to pyrophosphorylation in order to obtain TPP. In P. falciparum the phosphatase capable to catalyse this reaction has been identified by analysis of the substrate specificity. The recombinant enzyme accepts beside vitamin B1 also nucleotides, phosphorylated sugars and the B6 vitamer pyridoxal 5'-phosphate. Vitamin B1 biosynthesis is known to occur in the cytosol. The cytosolic localisation of this phosphatase was verified by transfection of a GFP chimera construct. Stage specific Northern blot analysis of the phosphatase clearly identified an expression profile throughout the entire erythrocytic life cycle of P. falciparum and thereby emphasises the importance of dephosphorylation reactions within the malaria parasite.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.molbiopara.2007.10.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Diverse Binding Modes Explain the Nanomolar Levels of Inhibitory Activities Against 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase from Exhibited by Reverse Hydroxamate Analogs of Fosmidomycin with Varying -Substituents.
Molecules
December 2024
School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against DXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the -phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of DXR.
View Article and Find Full Text PDFLow prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola.
Malar J
January 2025
Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008, Lisbon, Portugal.
Background: Malaria is the parasitic disease with the highest global morbidity and mortality. According to estimates from the World Health Organization (WHO), there were around 249 million cases in 2022, with 3.4% occurring in Angola.
View Article and Find Full Text PDFThe Ivermectin Related Compound Moxidectin Can Target Apicomplexan Importin α and Limit Growth of Malarial Parasites.
Cells
January 2025
Nuclear Signaling Laboratory, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Signal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily is crucial for eukaryotic function, with inhibitors targeting IMPα being of key interest as anti-infectious agents, including against the apicomplexan species and , causative agents of malaria and toxoplasmosis, respectively. We recently showed that the FDA-approved macrocyclic lactone ivermectin, as well as several other different small molecule inhibitors, can specifically bind to and inhibit and IMPα functions, as well as limit parasite growth. Here we focus on the FDA-approved antiparasitic moxidectin, a structural analogue of ivermectin, for its IMPα-targeting and anti-apicomplexan properties for the first time.
View Article and Find Full Text PDFGossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates.
Sci Rep
January 2025
West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana.
Gossypol has demonstrated significant antimalarial activity against chloroquine-resistant and susceptible Plasmodium falciparum parasites. However, data on its potency in clinical isolates of P. falciparum remains limited.
View Article and Find Full Text PDFDistinct immunogenicity outcomes of DNA vaccines encoding malaria transmission-blocking vaccine target antigens Pfs230D1M and Pvs230D1.
Vaccine
January 2025
Department of Global Health, George Washington University, Washington, D.C., USA. Electronic address:
Transmission-blocking vaccines (TBVs) targeting sexual-stage antigens represent a critical tool for malaria control and elimination through inhibiting parasite development within mosquitoes. P230, displayed on the surface of gametocytes and gametes, plays a crucial role in gamete fertilization and is one of the leading TBV candidates for both Plasmodium falciparum and P. vivax.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!