title: Effect of mutations found in carbohydrate-deficient glycoprotein syndrome type IA on the activity of phosphomannomutase 2.
abstract: 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.
authors.affiliation: Laboratory of Physiological Chemistry, ICP and Université Catholique de Louvain, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Pirard
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: L
authors.initials: L
authors.lastname: Heykants
authors.forename: E
authors.initials: E
authors.lastname: Schollen
authors.forename: S
authors.initials: S
authors.lastname: Grünewald
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: E
authors.initials: E
authors.lastname: van Schaftingen
mesh_terms: D019943:Amino Acid Substitution; D003001:Cloning, Molecular; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology* / Q000235:genetics*; D004795:Enzyme Stability; D004926:Escherichia coli; D005347:Fibroblasts / Q000201:enzymology; D005838:Genotype; D006720:Homozygote; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D017875:Phosphotransferases (Phosphomutases) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011994:Recombinant Proteins; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase