ARSA removes sulfate from PSAP(195-273):Sulfatide

Stable Identifier
Reaction [transition]
Homo sapiens
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Arylsulfatase A (ARSA) hydrolyses a sulfatide (cerebroside 3-sulfate, SM4) to form a cerebroside and sulfate Stinshoff & Jatzkewitz, 1975). Saposin B (PSAP(195-273)) is a promiscuous lipid-binding and transfer protein and an essential cofactor for the lysosomal hydrolysis of sulfatide by ARSA. It binds sulfatides in soluble stoichiometric complexes, which ARSA recognizes as substrates (Fischer & Jatzkewitz, 1975). ARSA is present in the lysosomal lumen and comprises two chains, components B and C, linked by disulfide bonds (Stein et al. 1989, Fujii et al. 1992). The conversion to 3-oxoalanine (formylglycine, FGly) of a cysteine residue is critical for catalytic activity in all eukaryotes (Chruszcz et al. 2003, Lukatela et al. 1998).
Defects in ARSA are a cause of metachromatic leukodystrophy (MLD) (MIM:250100), characterized by lysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues (Gieselmann et al. 1991, Polten et al. 1991). Arylsulfatase A activity is reduced in multiple sulfatase deficiency (MSD) (MIM:272200), a disorder characterized by decreased activity of sulfatases. The defect is due to the lack of post-translational modification of the critical cysteine needed for activity (Schmidt et al. 1995). In metachromatic leukodystrophy due to saposin B deficiency (MLDSAPB, MIM:249290) sulfatide accumulates because of the missing cofactor saposin B (Regis et al., 1999).
Literature References
PubMed ID Title Journal Year
239890 The activator of cerebroside sulphatase. Purification from human liver and identification as a protein

Jatzkewitz, H, Fischer, G

Hoppe Seylers Z Physiol Chem 1975
1670590 Molecular basis of different forms of metachromatic leukodystrophy

Polten, A, Kappler, J, Gieselmann, V, Fluharty, AL, von Figura, K, Fluharty, CB

N Engl J Med 1991
2562955 Cloning and expression of human arylsulfatase A

Pohlmann, R, Stein, C, Gieselmann, V, O'Brien, JS, Meyer, HE, von Figura, K, Waheed, A, Kreysing, J, Schmidt, B

J Biol Chem 1989
235289 Comparison of the cerebroside sulphatase and the arylsulphatase activity of human sulphatase A in the absence of activators

Stinshoff, K, Jatzkewitz, H

Biochim Biophys Acta 1975
9521684 Crystal structure of human arylsulfatase A: the aldehyde function and the metal ion at the active site suggest a novel mechanism for sulfate ester hydrolysis

Krauss, N, Selmer, T, Gieselmann, V, Saenger, W, von Figura, K, Lukatela, G, Theis, K

Biochemistry 1998
10196694 An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity

Gatti, R, Caroli, F, Keulemans, JL, van Diggelen, OP, Corsolini, F, Filocamo, M, Regis, S

Eur J Hum Genet 1999
1352993 Proteolytic processing of human lysosomal arylsulfatase A

Gasa, S, Makita, A, Shimizu, T, Kobayashi, T, Fujii, T, Honke, K, Ishikawa, M

Biochim Biophys Acta 1992
7628016 A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency

Selmer, T, Ingendoh, A, von Figura, K, Schmidt, B

Cell 1995
1678251 Mutations in the arylsulfatase A pseudodeficiency allele causing metachromatic leukodystrophy

Gieselmann, V, Fluharty, AL, von Figura, K, T√łnnesen, T

Am J Hum Genet 1991
12888274 Crystal structure of a covalent intermediate of endogenous human arylsulfatase A

Lebioda, L, Lewinski, K, Laidler, P, Ortlund, E, Monkiewicz, M, Chruszcz, M

J Inorg Biochem 2003
Catalyst Activity

cerebroside-sulfatase activity of active ARSA:Ca2+ [lysosomal lumen]

Orthologous Events
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