Formylglycine generating enzyme C336S mutant covalently bound to substrate peptide CTPSR
[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.    [ARSA_HUMAN] Defects in ARSA are a cause of leukodystrophy metachromatic (MLD) [MIM:250100]. MLD is a disease due to a lysosomal storage defect. It is characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues, with a diffuse loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Three forms of the disease can be distinguished according to the age at onset: late-infantile, juvenile and adult.                                         Arylsulfatase A activity is defective in multiple sulfatase deficiency (MSD) [MIM:272200]. 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. Note=Arylsulfatase A activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations result in defective post-translational modification of ARSA at residue Cys-69 that is not converted to 3-oxoalanine. 
[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.  [ARSA_HUMAN] Hydrolyzes cerebroside sulfate.
Publication Abstract from PubMed
The formylglycine (FGly)-generating enzyme (FGE) uses molecular oxygen to oxidize a conserved cysteine residue in all eukaryotic sulfatases to the catalytically active FGly. Sulfatases degrade and remodel sulfate esters, and inactivity of FGE results in multiple sulfatase deficiency, a fatal disease. The previously determined FGE crystal structure revealed two crucial cysteine residues in the active site, one of which was thought to be implicated in substrate binding. The other cysteine residue partakes in a novel oxygenase mechanism that does not rely on any cofactors. Here, we present crystal structures of the individual FGE cysteine mutants and employ chemical probing of wild-type FGE, which defined the cysteines to differ strongly in their reactivity. This striking difference in reactivity is explained by the distinct roles of these cysteine residues in the catalytic mechanism. Hitherto, an enzyme-substrate complex as an essential cornerstone for the structural evaluation of the FGly formation mechanism has remained elusive. We also present two FGE-substrate complexes with pentamer and heptamer peptides that mimic sulfatases. The peptides isolate a small cavity that is a likely binding site for molecular oxygen and could host reactive oxygen intermediates during cysteine oxidation. Importantly, these FGE-peptide complexes directly unveil the molecular bases of FGE substrate binding and specificity. Because of the conserved nature of FGE sequences in other organisms, this binding mechanism is of general validity. Furthermore, several disease-causing mutations in both FGE and sulfatases are explained by this binding mechanism.
A general binding mechanism for all human sulfatases by the formylglycine-generating enzyme.,Roeser D, Preusser-Kunze A, Schmidt B, Gasow K, Wittmann JG, Dierks T, von Figura K, Rudolph MG Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):81-6. Epub 2005 Dec 20. PMID:16368756
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.