Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme.

Abstract

C(alpha)-formylglycine (FGly) is the catalytic residue in the active site of eukaryotic sulfatases. It is posttranslationally generated from a cysteine in the endoplasmic reticulum. The genetic defect of FGly formation causes multiple sulfatase deficiency (MSD), a lysosomal storage disorder. We purified the FGly generating enzyme (FGE) and identified its gene and nine mutations in seven MSD patients. In patient fibroblasts, the activity of sulfatases is partially restored by transduction of FGE encoding cDNA, but not by cDNA carrying an MSD mutation. The gene encoding FGE is highly conserved among pro- and eukaryotes and has a paralog of unknown function in vertebrates. FGE is localized in the endoplasmic reticulum and is predicted to have a tripartite domain structure.

• Authors: Thomas Dierks, Bernhard Schmidt, Ljudmila V Borissenko, Jianhe Peng, Andrea Preusser, Malaiyalam Mariappan, Kurt von Figura
• Journal: Cell (Cell) Vol. 113 Issue 4 Pg. 435-44 (May 16 2003) ISSN: 0092-8674 [Print] United States
• PMID: 12757705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Enzymes
• C(alpha)-formylglycine
• Sulfatases
• Alanine
• Glycine

Topics

• Alanine (analogs & derivatives, biosynthesis, genetics)
• Amino Acid Sequence (genetics)
• Animals
• Base Sequence (genetics)
• Biological Assay
• CHO Cells
• Cattle
• Chromosomes, Human, Pair 3 (genetics)
• Cricetinae
• DNA, Complementary (analysis, genetics)
• Endoplasmic Reticulum (genetics, metabolism)
• Enzymes (genetics, isolation & purification)
• Gene Expression Regulation, Enzymologic (genetics)
• Genetic Vectors
• Glycine (analogs & derivatives, biosynthesis, genetics)
• Humans
• Mice
• Molecular Sequence Data
• Mutation (genetics)
• Protein Structure, Tertiary (genetics)
• Sphingolipidoses (enzymology, genetics)
• Sulfatases (deficiency, genetics)
• Transduction, Genetic