Shams-Eldin Hosam, de Macedo Cristiana Santos, Niehus Sebastian, Dorn Caroline, Kimmel Jürgen, Azzouz Nahid, Schwarz Ralph T
Institute for Virology, Laboratory of Parasitology, Medical Centre for Hygiene and Medical Microbiology, Philipps University, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
Biochem Biophys Res Commun. 2008 Jun 6;370(3):388-93. doi: 10.1016/j.bbrc.2008.03.033. Epub 2008 Mar 18.
Dolichol phosphate mannose synthase (DPM) catalyzes the reaction between dolichol phosphate (Dol-P) and guanosine diphosphate mannose (GDP-Man) to form dolichol-phosphate-mannose (Dol-P-Man). This molecule acts as mannose donor for N-glycosylation and glycosylphosphatidylinositol (GPI) biosynthesis. The Plasmodium falciparum DPM1 (Pfdpm1) possesses a single predicted transmembrane region near the N-, but not the C-terminus. Here we show that the cloned Pfdpm1 gene failed to complement a Saccharomyces cerevisiae mutant indicating that the parasite gene does not belong to the baker's yeast group, as was previously assumed. Furthermore, Pfdpm1 was unable to complement a mouse mutant deficient in DPM but efficiently complements the Schizosaccharomyces pombe fission yeast mutant, indicating a difference between fission yeast and mammalian DPM genes. Therefore, we reanalyzed the hydrophobicity scales of all known DPMs and consequently reclassify the DPM clade into six major novel subgroups. Furthermore, we show that Pfdpm1 represents a unique enzyme among these subgroups.
多萜醇磷酸甘露糖合酶（DPM）催化多萜醇磷酸（Dol-P）与鸟苷二磷酸甘露糖（GDP-Man）之间的反应，形成多萜醇磷酸甘露糖（Dol-P-Man）。该分子作为N-糖基化和糖基磷脂酰肌醇（GPI）生物合成的甘露糖供体。恶性疟原虫DPM1（Pfdpm1）在靠近N端而非C端处有一个预测的单一跨膜区域。在这里，我们表明克隆的Pfdpm1基因不能互补酿酒酵母突变体，这表明该寄生虫基因不属于面包酵母组，与之前的假设不同。此外，Pfdpm1不能互补缺乏DPM的小鼠突变体，但能有效地互补粟酒裂殖酵母突变体，这表明裂殖酵母和哺乳动物DPM基因之间存在差异。因此，我们重新分析了所有已知DPM的疏水性尺度，并相应地将DPM进化枝重新分类为六个主要的新亚组。此外，我们表明Pfdpm1在这些亚组中代表一种独特的酶。
