title: Mutations responsible for 3-phosphoserine phosphatase deficiency.
abstract: We report the identification of the mutations in the only known case of L-3-phosphoserine phosphatase deficiency, a recessively inherited condition. The two mutations correspond to the replacement of the semiconserved Asp32 residue by an asparagine and of the extremely conserved Met52 by a threonine. The effects of both mutations were studied on the human recombinant enzyme, expressed in Escherichia coli. Met52Thr almost abolished the enzymatic activity, whereas the Asp32Asn mutation caused a 50% decrease in Vmax. In addition, L-serine, which inhibits the conversion of [(14)C] phosphoserine to serine when catalysed by the wild-type enzyme, had a lesser inhibitory effect on the Asp32Asn mutant, indicating a reduction in the rate of phosphoenzyme hydrolysis. These modifications in the properties of the enzyme are consistent with the modification in the kinetic properties observed in fibroblasts from the patient.
authors.affiliation: 1Laboratory of Physiological Chemistry, Institute of Cellular Pathology (ICP) and Université catholique de Louvain, Brussels, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Veiga-da-Cunha
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Collet
authors.forename: Benoît
authors.initials: B
authors.lastname: Prieur
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.forename: Yves
authors.initials: Y
authors.lastname: Peeraer
authors.forename: Anja
authors.initials: A
authors.lastname: Rabbijns
authors.forename: Emile
authors.initials: E
authors.lastname: Van Schaftingen
mesh_terms: D000595:Amino Acid Sequence; D018076:DNA, Complementary; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D011994:Recombinant Proteins; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase