Guanosine triphosphate cyclohydrolase in Plasmodium falciparum and other Plasmodium species |
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Authors: | J Krungkrai Y Yuthavong H K Webster |
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Institution: | 1. Department of Biochemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand;2. Department of Immunology and Biochemistry, Armed Forces Research Institute of Medical Sciences, Rajavithi Road, Bangkok 10400, Thailand |
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Abstract: | GTP cyclohydrolase (EC 3.5.4.16), the first enzyme in the pteridine pathway leading to the de novo formation of folic acid, has been identified and isolated from the human malaria parasite, Plasmodium falciparum. The enzyme was purified 200-fold by high performance size-exclusion chromatography on a TSK-G-3000 SW protein column. The molecular weight was estimated at 300 000. Optimal enzyme activity was observed at pH 8.0 and 42 degrees C. The Km for GTP was 54.6 microM. Products of the enzyme reaction were identified as the carbon-8 of GTP and D-erythro-dihydroneopterin triphosphate. ATP was a competitive inhibitor (Ki = 600 microM) of the enzyme. Activity of the enzyme was Mg2+-independent, whereas Mn2+, Cu2+ and Hg2+ (5 mM) were inhibitory. GTP cyclohydrolase activity was also identified in a murine parasite, Plasmodium berghei, and a simian parasite, Plasmodium knowlesi. Activity of the enzyme in P. knowlesi, an intrinsically synchronous quotidian parasite, was found to be dependent on the stage of parasite development. |
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Keywords: | GTP cyclohydrolase Pteridines Folates ATP adenosine 5′-triphosphate EDTA ethylenediamine tetraacetic acid FPG folylpolyglutamate GluDH glutamate dehydrogenase GTP guanosine 5′-triphosphate HPLC high-performance liquid chromatography HPSEC high-performance size-exclusion chromatography PABA 4-aminobenzoic acid TLC thin-layer chromatography |
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