Biomaterial Database

Divergent regulation of dihydrofolate reductase between malaria parasite and human host. 2002

Kai Zhang, and Pradipsinh K Rathod

Department of Biology, The Catholic University of America, Washington, DC 20064, USA.

For half a century, successful antifolate therapy against Plasmodium falciparum malaria has been attributed to host-parasite differences in drug binding to dihydrofolate reductase-thymidylate synthase (DHFR-TS). Selectivity may also arise through previously unappreciated differences in regulation of this drug target. The DHFR-TS of Plasmodium binds its cognate messenger RNA (mRNA) and inhibits its own translation. However, unlike translational regulation of DHFR or TS in humans, DHFR-TS mRNA binding is not coupled to enzyme active sites. Thus, antifolate treatment does not relieve translational inhibition and parasites cannot replenish dead enzyme.

UI	MeSH Term	Description	Entries
D009097	Multienzyme Complexes	Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.	Complexes, Multienzyme
D010963	Plasmodium falciparum	A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.	Plasmodium falciparums,falciparums, Plasmodium
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005493	Folic Acid Antagonists	Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)	Antifolate,Antifolates,Dihydrofolate Reductase Inhibitor,Folic Acid Antagonist,Dihydrofolate Reductase Inhibitors,Folic Acid Metabolism Inhibitors,Acid Antagonist, Folic,Acid Antagonists, Folic,Antagonist, Folic Acid,Antagonists, Folic Acid,Inhibitor, Dihydrofolate Reductase,Inhibitors, Dihydrofolate Reductase,Reductase Inhibitor, Dihydrofolate,Reductase Inhibitors, Dihydrofolate
D006790	Host-Parasite Interactions	The relationship between an invertebrate and another organism (the host), one of which lives at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically.	Host-Parasite Relations,Parasite-Host Relations,Host-Parasite Relationship,Parasite-Host Interactions,Host Parasite Interactions,Host Parasite Relations,Host Parasite Relationship,Host-Parasite Interaction,Host-Parasite Relation,Host-Parasite Relationships,Interaction, Host-Parasite,Interaction, Parasite-Host,Interactions, Host-Parasite,Interactions, Parasite-Host,Parasite Host Interactions,Parasite Host Relations,Parasite-Host Interaction,Parasite-Host Relation,Relation, Host-Parasite,Relation, Parasite-Host,Relations, Host-Parasite,Relations, Parasite-Host,Relationship, Host-Parasite,Relationships, Host-Parasite
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000962	Antimalarials	Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)	Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated