HUMAN AND SACCHAROMYCES-CEREVISIAE DOLICHOL PHOSPHATE MANNOSE SYNTHASES REPRESENT 2 CLASSES OF THE ENZYME, BUT BOTH FUNCTION IN SCHIZOSACCHAROMYCES-POMBE

Dolichol phosphate mannose (Dol-P-Man), formed upon transfer of Man fr om GDPMan to Dol-P, is a mannosyl donor in pathways leading to N-glyco sylation, glycosyl phosphatidylinositol membrane anchoring, and O-mann osylation of protein, Dol-P-Man synthase is an essential protein in Sa ccharomyces cerevisiae. We have cloned cDNAs encoding human and Schizo saccharomyces pombe proteins that resemble S. cerevisiae Dol-P-Man syn thase, Disruption of the gene for the S. pombe Dol-P-Man synthase homo log, dpm1(+), is lethal, The known Dol-P-Man synthase sequences can be divided into two classes, One contains the S. cerevisiae, Ustilago ma ydis, and Trypanosoma brucei enzymes, which have a COOH-terminal hydro phobic domain, and the other contains the human, S. pombe, and Caenorh abditis synthases, which lack a hydrophobic COOH-terminal domain, The two classes of synthase are functionally equivalent, because S. cerevi siae DPM1 and its human counterpart both complement the lethal null mu tation in S. pombe dpm1(+), The findings that Dol-P-Man synthase is es sential in yeast and that the Ustilago and Trypanosoma synthases are i n a different class from the human enzyme raise the possibility that D ol-P-Man synthase could be exploited as a target for inhibitors of pat hogenic eukaryotic microbes.