Characterization of three genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum

C. S. Lee, E. Salcedo, Q. Wang, P. Wang, P. F. Sims, J. E. Hyde

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Although the folate metabolic pathway in malaria parasites is a major chemotherapeutic target, resistance to currently available antifolate drugs is an increasing problem. This pathway, however, includes a number of enzymes that, to date, have not been characterized despite their potential for clinical exploitation. As a step towards evaluation of additional targets in this pathway, we report the isolation and characterization of 3 new genes that encode homologues of GTP cyclohydrolase I (GTP-CH), dihydrofolate synthase/folylpolyglutamate synthase (DHFS/FPGS) and serine hydroxymethyltransferase (SHMT). The genes encoding GTP-CH and SHMT are unambiguously assigned to chromosome 12, while that for DHFS/FPGS is tentatively assigned to chromosome 13. All 3 genes are expressed in blood-stage parasites, yielding transcripts of which only ca 60-70% is accounted for by coding sequence. All 3 of the proteins predicted to be encoded by these genes display sequence differences compared to the human host homologues that may be of functional significance. These data bring the complement of cloned genes that encode activities in the pathway to seven, leaving only the gene encoding dihydroneopterin aldolase (DHNA) to be identified in the route from GTP to folate synthesis and folate turnover in the thymidylate cycle.
    Original languageEnglish
    Pages (from-to)1-13
    Number of pages12
    JournalParasitology
    Volume122
    Issue number1
    DOIs
    Publication statusPublished - 2001

    Keywords

    • Dihydrofolate synthase
    • Folate biosynthesis
    • Folylpolyglutamate synthase
    • GTP cyclohydrolase
    • Malaria
    • Serine hydroxymethyltransferase

    Fingerprint

    Dive into the research topics of 'Characterization of three genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum'. Together they form a unique fingerprint.

    Cite this