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 [14C] 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.
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Acknowledgements
MVDC is Chercheur qualifié and JFC is Chargé de recherche of the Belgian Fonds National de la Recherche Scientifique, and AR postdoctoral fellow of the Fund for Scientific Research-Flanders (Belgium). This work was supported by the Belgian Federal Service for Scientific, Technical and Cultural Affairs and the Fonds National de la Recherche Scientifique (grants to EVS).
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Veiga-da-Cunha, M., Collet, JF., Prieur, B. et al. Mutations responsible for 3-phosphoserine phosphatase deficiency. Eur J Hum Genet 12, 163–166 (2004). https://doi.org/10.1038/sj.ejhg.5201083
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DOI: https://doi.org/10.1038/sj.ejhg.5201083
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