Cloning of Plasmodium falciparum protein disulfide isomerase homologue by affinity purification using the antiplasmodial inhibitor 1,4-bis[3-[N-(cyclohexyl methyl)amino]propyl]piperazine..
A series of 10 1,4-bis(3-aminopropyl)piperazine compounds was found to display antiplasmodial activity with 50% growth inhibition between 30 and 250 nM, on three Plasmodium falciparum strains differently sensitive to chloroquine. By affinity chromatography using one of these compounds, a 52-kDa protein was isolated from P. falciparum, microsequenced and cloned. It corresponded to a single copy gene encoding a 453 amino acid protein displaying the typical features of protein disulfide isomerases, a thiol metabolizing enzyme belonging to the thiol: disulfide oxidoreductase superfamily, which was not previously described in malarial species.
Florent
I
I
Laboratoire de Biologie et Evolution des Parasites, FR CNRS 63, Muséum National d'Histoire Naturelle, Paris, France.
Mouray
E
E
Dali Ali
F
F
Drobecq
H
H
Girault
S
S
Schrével
J
J
Sergheraert
C
C
Grellier
P
P
Florenta
I
I
D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents; D001483:Base Sequence; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D003105:Colombia; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D019704:Protein Disulfide-Isomerases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013636:Tanzania; D013785:Thailand
D000981:Antiprotozoal Agents; D011994:Recombinant Proteins; D019704:Protein Disulfide-Isomerases