Comparative characterization of hexose transporters of Plasmodium knowlesi, Plasmodium yoelii and Toxoplasma gondii highlights functional differences within the apicomplexan family
| Autor: | Timothy T. Stedman, Clemens H. M. Kocken, Alan W. Thomas, Sanjeev Krishna, Thierry Joët, Lennart Holterman, Annemarie van der Wel |
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| Rok vydání: | 2002 |
| Předmět: |
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Complementary Xenopus Glucose uptake Molecular Sequence Data Fructose Transfection Binding Competitive Biochemistry Substrate Specificity parasitic diseases Animals Plasmodium knowlesi Hexose Amino Acid Sequence Cloning Molecular Molecular Biology Phylogeny Hexoses chemistry.chemical_classification Dose-Response Relationship Drug Sequence Homology Amino Acid biology Temperature Glucose transporter Toxoplasma gondii Biological Transport Transporter Plasmodium falciparum Plasmodium yoelii Cell Biology biology.organism_classification Kinetics Glucose chemistry Oocytes Plasmodium vivax Toxoplasma Research Article |
| Zdroj: | Biochemical Journal. 368:923-929 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20021189 |
| Popis: | Chemotherapy of apicomplexan parasites is limited by emerging drug resistance or lack of novel targets. PfHT1, the Plasmodium falciparum hexose transporter 1, is a promising new drug target because asexual-stage malarial parasites depend wholly on glucose for energy. We have performed a comparative functional characterization of PfHT1 and hexose transporters of the simian malarial parasite P. knowlesi (PkHT1), the rodent parasite P. yoelii (PyHT1) and the human apicomplexan parasite Toxoplasma gondii ( T. gondii glucose transporter 1, TgGT1). PkHT1 and PyHT1 share >70% amino acid identity with PfHT1, while TgGT1 is more divergent (37.2% identity). All transporters mediate uptake of D-glucose and D-fructose. PyHT1 has an affinity for glucose ( K (m) approximately 0.12 mM) that is higher than that for PkHT1 ( K (m) approximately 0.67 mM) or PfHT1 ( K (m) approximately 1 mM). TgGT1 is highly temperature dependent (the Q (10) value, the fold change in activity for a 10 degrees C change in temperature, was >7) compared with Plasmodium transporters ( Q (10), 1.5-2.5), and overall has the highest affinity for glucose ( K (m) approximately 30 microM). Using active analogues in competition for glucose uptake, experiments show that hydroxyl groups at the C-3, C-4 and C-6 positions are important in interacting with PkHT1, PyHT1 and TgGT1. This study defines models useful to study the biology of apicomplexan hexose permeation pathways, as well as contributing to drug development. |
| Databáze: | OpenAIRE |
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