Phosphomannose isomerase (PMI) is a monomeric enzyme that converts fructose-6- P (Fru-6-P) and mannose-6-P (Man-6-P). It is the only known link between glucose catabolism and mannose activation for glycosylation. Man-6-P can also be produced directly via hexokinase from mannose. The enzyme has been purified, crystallized, and its structure determined (Gracy and Noltmann 1968; Proudfoot et al. 1994a,b; Cleasby et al. 1996). The genes have been cloned from several organisms. Loss of PMI is lethal in yeast (Smith et al. 1992) and causes a congenital disorder of glycosylation (CDG-Ib) in humans (Niehues et al. 1998; Freeze and Aebi 1999), but both can be rescued by providing exogenous mannose. Because loss of PMI is lethal in yeast, highly specific inhibitors of Candida albicans PMI were sought, as patients with acquired immunodeficiency disease (AIDS) frequently have serious C. albicans infections. No specific inhibitors have been found.
KeywordsXanthomonas Campestris Phosphomannose Isomerase Mannose Phosphate Isomerase Glycoprotein Syndrome Type Mannose Therapy
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- Niehues R, Hasilik M, Alton G, Korner C, Schiebe-Sukumar M, Koch HG, Zimmer KP, Wu R, Harms E, Reiter K, von Figura K, Freeze HH, Harms HK, Marquardt T (1998) Carbohydrate-deficient glycoprotein syndrome type Ib: phosphomannose isomerase deficiency and mannose therapy. J Clin Invest 101:1414–1420PubMedCrossRefGoogle Scholar