A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency

Cell. 1995 Jul 28;82(2):271-8. doi: 10.1016/0092-8674(95)90314-3.

Abstract

Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder characterized by a decreased activity of all known sulfatases. The deficiency of sulfatases was proposed to result from the lack of a co- or posttranslational modification that is common to all sulfatases and required for their catalytic activity. Structural analysis of two catalytically active sulfatases revealed that a cysteine residue that is predicted from the cDNA sequence and conserved among all known sulfatases is replaced by a 2-amino-3-oxopropionic acid residue, while in sulfatases derived from MSD cells, this cysteine residue is retained. It is proposed that the co- or posttranslational conversion of a cysteine to 2-amino-3-oxopropionic acid is required for generating catalytically active sulfatases and that deficiency of this protein modification is the cause of MSD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Aldehydes*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Conserved Sequence
  • Cysteine*
  • DNA, Complementary
  • Fibroblasts / enzymology
  • Humans
  • Lysosomal Storage Diseases / enzymology
  • Lysosomal Storage Diseases / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Sequence Homology, Amino Acid
  • Sulfatases / deficiency*
  • Sulfatases / genetics*
  • Sulfatases / isolation & purification

Substances

  • 2-amino-3-oxopropionic acid
  • Aldehydes
  • DNA, Complementary
  • Sulfatases
  • Cysteine
  • Alanine