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Functional Analysis of the First Mannosyltransferase (PIG-M) involved in Glycosylphosphatidylinositol Synthesis in Plasmodium falciparum  

Kim, Youn Uck (Department of Biological Sciences, Sun Moon University)
Hong, Yeongjin (Genomic Research Center for Enteropathogenic Bacteria and Department of Microbiology, Chonnam National University Medical School)
Publication Information
Molecules and Cells / v.24, no.2, 2007 , pp. 294-300 More about this Journal
Abstract
The mammalian glycosylphosphatidylinositol (GPI) anchor consists of three mannoses attached to acylated GlcN-(acyl)PI to form $Man_3$-GlcN-(acyl)PI. The first of the three mannose groups is attached to an intermediate to generate Man-GlcN-(acyl)PI by the first mannosyltransferase (GPI-MT-I). Mammalian and protozoan GPI-MT-I have different substrate specificities. PIG-M encodes the mammalial GPI-MT-I which has 423 amino acids and multiple transmembrane domains. In this work we cloned PIG-M homologues from humans, Plasmodium falciparum (PfPIG-M), and Saccharomyces cerevisiae (GPI14), to test whether they could complement GPI-MT-I-deficient mammalian cells, since this biosynthetic step is likely to be a good target for selective screening of inhibitors against many pathogenic organisms. PfPIG-M partially restored cell surface expression of the GPI-anchored protein CD59 in PIG-M deficient mammalian cells, and first mannose transfer activity in vitro; however, this was not the case for GPI14.
Keywords
GPI; GPI-MT-I; PIG-M; Plasmodium falciparum; Saccharomyces cerevisiae;
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