5ssx

Structural highlights

Disease

SUMF1_HUMAN Defects in SUMF1 are the cause of multiple sulfatase deficiency (MSD) [MIM:272200. MSD is a clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay. Inheritance is autosomal recessive.^{[1] [2] [3] [4]}

Function

SUMF1_HUMAN Using molecular oxygen and an unidentified reducing agent, oxidizes a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also called C(alpha)-formylglycine. Known substrates include GALNS, ARSA, STS and ARSE.^{[5] [6]}

See Also

• Sulfatase-modifying factor

References

1. ↑ Cosma MP, Pepe S, Annunziata I, Newbold RF, Grompe M, Parenti G, Ballabio A. The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell. 2003 May 16;113(4):445-56. PMID:12757706
2. ↑ Dierks T, Schmidt B, Borissenko LV, Peng J, Preusser A, Mariappan M, von Figura K. Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme. Cell. 2003 May 16;113(4):435-44. PMID:12757705
3. ↑ Cosma MP, Pepe S, Parenti G, Settembre C, Annunziata I, Wade-Martins R, Di Domenico C, Di Natale P, Mankad A, Cox B, Uziel G, Mancini GM, Zammarchi E, Donati MA, Kleijer WJ, Filocamo M, Carrozzo R, Carella M, Ballabio A. Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency. Hum Mutat. 2004 Jun;23(6):576-81. PMID:15146462 doi:10.1002/humu.20040
4. ↑ Schlotawa L, Steinfeld R, von Figura K, Dierks T, Gartner J. Molecular analysis of SUMF1 mutations: stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency. Hum Mutat. 2008 Jan;29(1):205. PMID:18157819 doi:10.1002/humu.9515
5. ↑ Cosma MP, Pepe S, Annunziata I, Newbold RF, Grompe M, Parenti G, Ballabio A. The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell. 2003 May 16;113(4):445-56. PMID:12757706
6. ↑ Preusser-Kunze A, Mariappan M, Schmidt B, Gande SL, Mutenda K, Wenzel D, von Figura K, Dierks T. Molecular characterization of the human Calpha-formylglycine-generating enzyme. J Biol Chem. 2005 Apr 15;280(15):14900-10. Epub 2005 Jan 18. PMID:15657036 doi:M413383200