1fsu

Structural highlights

Disease

[ARSB_HUMAN] Defects in ARSB are the cause of mucopolysaccharidosis type 6 (MPS6) [MIM:253200]; also known as Maroteaux-Lamy syndrome. MPS6 is an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of dermatan sulfate. Clinical features can include abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly, and cardiac abnormalities. A wide variation in clinical severity is observed.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]} Arylsulfatase B 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 B activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations result in defective post-translational modification of ARSB at residue Cys-91 that is not converted to 3-oxoalanine.^{[11] [12]}

Function

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Wicker G, Prill V, Brooks D, Gibson G, Hopwood J, von Figura K, Peters C. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). An intermediate clinical phenotype caused by substitution of valine for glycine at position 137 of arylsulfatase B. J Biol Chem. 1991 Nov 15;266(32):21386-91. PMID:1718978
2. ↑ Jin WD, Jackson CE, Desnick RJ, Schuchman EH. Mucopolysaccharidosis type VI: identification of three mutations in the arylsulfatase B gene of patients with the severe and mild phenotypes provides molecular evidence for genetic heterogeneity. Am J Hum Genet. 1992 Apr;50(4):795-800. PMID:1550123
3. ↑ Isbrandt D, Arlt G, Brooks DA, Hopwood JJ, von Figura K, Peters C. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): six unique arylsulfatase B gene alleles causing variable disease phenotypes. Am J Hum Genet. 1994 Mar;54(3):454-63. PMID:8116615
4. ↑ Voskoboeva E, Isbrandt D, von Figura K, Krasnopolskaya X, Peters C. Four novel mutant alleles of the arylsulfatase B gene in two patients with intermediate form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Hum Genet. 1994 Mar;93(3):259-64. PMID:8125475
5. ↑ Simonaro CM, Schuchman EH. N-acetylgalactosamine-4-sulfatase: identification of four new mutations within the conserved sulfatase region causing mucopolysaccharidosis type VI. Biochim Biophys Acta. 1995 Dec 12;1272(3):129-32. PMID:8541342
6. ↑ Litjens T, Brooks DA, Peters C, Gibson GJ, Hopwood JJ. Identification, expression, and biochemical characterization of N-acetylgalactosamine-4-sulfatase mutations and relationship with clinical phenotype in MPS-VI patients. Am J Hum Genet. 1996 Jun;58(6):1127-34. PMID:8651289
7. ↑ Villani GR, Balzano N, Vitale D, Saviano M, Pavone V, Di Natale P. Maroteaux-lamy syndrome: five novel mutations and their structural localization. Biochim Biophys Acta. 1999 Feb 24;1453(2):185-92. PMID:10036316
8. ↑ Wu JY, Yang CF, Lee CC, Chang JG, Tsai FJ. A novel mutation (Q239R) identified in a Taiwan Chinese patient with type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome). Hum Mutat. 2000 Apr;15(4):389-90. PMID:10738004 doi:<389::AID-HUMU31>3.0.CO;2-0 10.1002/(SICI)1098-1004(200004)15:4<389::AID-HUMU31>3.0.CO;2-0
9. ↑ Yang CF, Wu JY, Lin SP, Tsai FJ. Mucopolysaccharidosis type VI: Report of two Taiwanese patients and identification of one novel mutation. J Formos Med Assoc. 2001 Dec;100(12):820-3. PMID:11802522
10. ↑ Karageorgos L, Harmatz P, Simon J, Pollard A, Clements PR, Brooks DA, Hopwood JJ. Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy. Hum Mutat. 2004 Mar;23(3):229-33. PMID:14974081 doi:10.1002/humu.10313
11. ↑ Schmidt B, Selmer T, Ingendoh A, von Figura K. A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency. Cell. 1995 Jul 28;82(2):271-8. PMID:7628016
12. ↑ 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
13. ↑ Bond CS, Clements PR, Ashby SJ, Collyer CA, Harrop SJ, Hopwood JJ, Guss JM. Structure of a human lysosomal sulfatase. Structure. 1997 Feb 15;5(2):277-89. PMID:9032078