Dihydroorotase of human malarial parasite Plasmodium falciparum differs from host enzyme.
Plasmodium falciparum, the causative agent of human malaria, is totally dependent on de novo pyrimidine biosynthetic pathway. A gene encoding P. falciparum dihydroorotase (pfDHOase) was cloned and expressed in Escherichia coli as monofunctional enzyme. PfDHOase revealed a molecular mass of 42kDa. In gel filtration chromatography, the major enzyme activity eluted at 40kDa, indicating that it functions in a monomeric form. This was similarly observed using the native enzyme purified from P. falciparum. Interestingly, kinetic parameters of the enzyme and inhibitory effect by orotate and its 5-substituted derivatives parallel that found in mammalian type I DHOase. Thus, the malarial enzyme shares characteristics of both type I and type II DHOases. This study provides the monofunctional property of the parasite DHOase lending further insights into its differences from the human enzyme which forms part of a multifunctional protein.
Krungkrai
Sudaratana R
SR
Department of Medical Science, Faculty of Science, Rangsit University, Patumthani 12000, Thailand.
Wutipraditkul
Nuchanat
N
Krungkrai
Jerapan
J
D000595:Amino Acid Sequence; D000818:Animals; D004080:Dihydroorotase / Q000737:chemistry*; D004789:Enzyme Activation; D004795:Enzyme Stability; D006801:Humans; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology*; D013379:Substrate Specificity
D004080:Dihydroorotase