Antibiotic inhibitors of organellar protein synthesis in Plasmodium falciparum.
Elongation factor Tu (EF-Tu) is encoded by the tuf gene of the plastid organelle of the malaria parasite Plasmodium falciparum. A range of structurally unrelated inhibitors of this GTP-dependent translation factor was shown to have antimalarial activity in blood cultures. The most active was the cyclic thiazolyl peptide amythiamicin A with an IC50 = 0.01 microM. Demonstrable complexes were formed in vitro between a recombinant version of P. falciparum EF-Tu(pl) and inhibitors that bind to different sites on EF-Tu; these included the antibiotics kirromycin, GE2270A and enacyloxin IIa.
Clough
B
B
National Institute for Medical Research, Mill Hill, London, UK.
Rangachari
K
K
Strath
M
M
Preiser
P R
PR
Wilson
R J
RJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D017125:Genes, Protozoan; D047028:Macrocyclic Compounds; D010444:Peptide Elongation Factor Tu / Q000037:antagonists & inhibitors / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D018087:Plastids / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011090:Polyenes / Q000378:metabolism / Q000494:pharmacology; D015800:Protozoan Proteins / Q000096:biosynthesis*; D011728:Pyridones / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D047028:Macrocyclic Compounds; D010456:Peptides, Cyclic; D011090:Polyenes; D015800:Protozoan Proteins; D011728:Pyridones; D011994:Recombinant Proteins; D013844:Thiazoles; C072734:enacyloxin IIa; C088498:amythiamicin A; D010444:Peptide Elongation Factor Tu; C068122:GE 2270 A; C008536:mocimycin