Effect of mutations found in carbohydrate-deficient glycoprotein syndrome type IA on the activity of phosphomannomutase 2

FEBS Lett. 1999 Jun 11;452(3):319-22. doi: 10.1016/s0014-5793(99)00673-0.


Seven mutant forms of human phosphomannomutase 2 were produced in Escherichia coli and purified. These mutants had a Vmax of 0.2-50% of the wild enzyme and were unstable. The least active protein (R141H) bears a very frequent mutation, which has never been found in the homozygous state whereas the second least active protein (D188G) corresponds to a mutation associated with a particularly severe phenotype. We conclude that total lack of phosphomannomutase 2 is incompatible with life. Another conclusion is that the elevated residual phosphomannomutase activity found in fibroblasts of some patients is contributed by their mutated phosphomannomutase 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Cloning, Molecular
  • Congenital Disorders of Glycosylation / enzymology*
  • Congenital Disorders of Glycosylation / genetics*
  • Enzyme Stability
  • Escherichia coli
  • Fibroblasts / enzymology
  • Genotype
  • Homozygote
  • Hot Temperature
  • Humans
  • Kinetics
  • Mutagenesis, Site-Directed
  • Phosphotransferases (Phosphomutases) / chemistry
  • Phosphotransferases (Phosphomutases) / genetics*
  • Phosphotransferases (Phosphomutases) / metabolism*
  • Point Mutation*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Thermodynamics


  • Recombinant Proteins
  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase