Mannose phosphate isomerase (MPI)

Abstract

Mannose phosphate isomerase or phosphomannose isomerase (MPI or PMI) belongs to the family of enzymes that reversibly converts aldoses and ketoses. In this case, it is fructose-6-P and mannose-6-P (Man-6-P). Man-6-P can be catabolized or used as a precursor for glycan synthesis. It is the only known physiological link between glucose and mannose metabolism. MPI genes have been cloned from many different organisms. Several of them have been expressed, purified, crystallized, and the structures were determined (Cleasby et al. 1996; Gracy and Noltmann 1968; Proudfoot et al. 1994). Loss of MPI is lethal in Saccharomyces cerevisiae (Smith et al. 1992) and causes a genetic disorder, congenital disorder of glycosylation (MPI-CDG or CDG-Ib) in humans (Freeze and Aebi 1999; Niehues et al. 1998), but both organisms can be rescued by providing exogenous mannose. Since loss of MPI is deleterious in yeast, highly specific inhibitors of Candida albicans MPI were sought since AIDS patients frequently have serious C. albicans infections.