Advertisement

Abstract

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.

Keywords

Xanthomonas Campestris Phosphomannose Isomerase Mannose Phosphate Isomerase Glycoprotein Syndrome Type Mannose Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alton G, Hasilik M, Niehues R, Panneerselvam K, Etchison JR, Fana F, Freeze HH (1998) Direct utilization of mannose for mammalian glycoprotein biosynthesis. Glycobiology 8:286–295CrossRefGoogle Scholar
  2. Cleasby AA, Wonacott, et al (1996) The X-ray crystal structure of phosphomannose isomerase from Candida albicans at 1.7 Å resolution. Nat Struct Biol 3:470–479PubMedCrossRefGoogle Scholar
  3. Freeze HH (1998) Disorders in protein glycosylation and potential therapy: tip of an iceberg? J Pediatr 133:593–600PubMedCrossRefGoogle Scholar
  4. Freeze HH, Aebi MM (1999) Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity. Biochim Biophys Acta 1455:167–178PubMedCrossRefGoogle Scholar
  5. Freinkel N, Lewis NJ, et al (1984) The honeybee syndrome: implications of the teratogenicity of mannose in rat-embryo culture. N Engl J Med 310:223–230PubMedCrossRefGoogle Scholar
  6. Gracy RW, Noltmann EA (1968) Studies on phosphomannose isomerase. I. Isolation, homogeneity measurements, and determination of some physical properties. J Biol Chem 243:3161–3168PubMedGoogle Scholar
  7. Jensen SO, Reeves PR (1998) Domain organisation in phosphomannose isomerases (type I and type II). Biochim Biophys Acta 1382:5–7PubMedCrossRefGoogle Scholar
  8. 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
  9. Panneerselvam K, Etchison JR, et al (1997) Human fibroblasts prefer mannose over glucose as a source of mannose for N-glycosylation: evidence for the functional importance of transported mannose. J Biol Chem 272:23123–23129PubMedCrossRefGoogle Scholar
  10. Proudfoot AE, Payton MA, Wells TN (1994a) Purification and characterization of fungal and mammalian phosphomannose isomerases. J Protein Chem 13:619–627PubMedCrossRefGoogle Scholar
  11. Proudfoot AE, Turcatti G, Wells TN, Payton MA, Smith DJ (1994b) Purification, cDNA cloning and heterologous expression of human phosphomannose isomerase. Eur J Biochem 219:415–423PubMedCrossRefGoogle Scholar
  12. Saunders SA, Gracy RW, Schnackerz KD, Noltmann EA (1969) Are honeybees deficient in phosphomannose isomerase? Science 164:858–859PubMedCrossRefGoogle Scholar
  13. Smith DJ, Proudfoot A, Friedli L, Klig LS, Paravicini G, Payton MA (1992) PMI40, an intron-containing gene required for early steps in yeast mannosylation. Mol Cell Biol 12:2924–2930PubMedGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Hudson H. Freeze
    • 1
  1. 1.Glyciobiology ProgramThe Burnham InstituteLa JollaUSA

Personalised recommendations