LSDDB

Multiple sulfatase disorder (MSD)

The type 1 sulfates are post transnationally modified and activated by the formyl glycine generating enzyme (FGE). FGE catalyzes the activation of sulfatases by the oxidation of an active site cysteine residue in the CXPXR motif to an fGLY (formyl glycine) residue. This activation is very important since sulfatases use the hydrated form of fGLY as the catalytic nucleophile. Therefore failure in post translational activation results in the global deficiency in the function of sulfatase enzymes (Miarzlou et al., 2019). The gene for the SUMF1 gene encoding FGE is located at 3p26.1 (Dierks et al., 2003).

Reference :
Dierks, T. et al. (2003) ‘Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme’, Cell, 113(4), pp. 435–444.
Miarzlou, D.A. et al. (2019) ‘Structure of formylglycine-generating enzyme in complex with copper and a substrate reveals an acidic pocket for binding and activation of molecular oxygen’, Chemical Science, 10(29), pp. 7049–7058. doi:10.1039/C9SC01723B.