Aryl sulfatase B
| Aryl sulfatase B | ||
|---|---|---|
|
||
| Ribbon model of aryl sulfatase B, according to PDB 1FSU | ||
| Properties of human protein | ||
| Mass / length primary structure | 497 amino acids | |
| Cofactor | Ca 2+ | |
| Identifier | ||
| Gene name | ARSB | |
| External IDs | ||
| Drug information | ||
| ATC code | A16 AB08 | |
| DrugBank | DB01279 | |
| Drug class | enzyme | |
| Enzyme classification | ||
| EC, category | 3.1.6.12 , sulfatase | |
| Response type | Elimination of sulphate | |
| Substrate | Chondroitin / dermatan sulfate + H 2 O | |
| Products | Chondroitin / Dermatan + sulfate | |
| Occurrence | ||
| Parent taxon | multicellular animals | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 411 | 11881 |
| Ensemble | ENSG00000113273 | ENSMUSG00000042082 |
| UniProt | P15848 | P50429 |
| Refseq (mRNA) | NM_000046 | NM_009712 |
| Refseq (protein) | NP_000037 | NP_033842 |
| Gene locus | Chr 5: 78.78 - 78.99 Mb | Chr 13: 93.77 - 93.94 Mb |
| PubMed search | 411 |
11881
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Aryl sulfatase B (also: N-acetylgalactosamine-4-sulfate sulfatase ) is the enzyme in animals that splits sulfate from the mucopolysaccharides chondroitin sulfate and dermatan sulfate. The breakdown of these macromolecules , which form the cartilage , takes place in the lysosomes of the cells . In humans, the enzyme activity does not exist or too little, as evidenced by mutations in ARSB - gene can be triggered, it comes through the accumulation of mucopolysaccharides in the lysosomes to a metabolic disorder , of mucopolysaccharidosis type VI ( Maroteaux-Lamy syndrome ) with skeletal malformations. Since 2006, this can be successfully treated with the help of enzyme replacement therapy with artificially produced enzyme ( Galsulfase , Biomarin Pharmaceutical).
Aryl sulfatase B is a sulfatase , an enzyme that splits off sulfate. The formylation of cysteine-91 to ketoalanine (a post-translational modification ) is critical for calcium cofactor capture and enzyme activity. A defect in this process affects multiple sulfatases and leads to multiple sulfatase deficiencies .
The effect of the anti-malarial drug chloroquine appears to be based in part on an inhibition of aryl sulfatase B. In addition to sulfatase activity, the enzyme appears to have regulatory effects in the interleukin-8 signaling pathway and on epithelial cell migration .
literature
- R. Giugliani, CG Carvalho et al. a .: Recent Advances in Treatment Approaches of Mucopolysaccharidosis VI. In: Current Pharmaceutical Biotechnology . Volume 12, Number 6, June 2011, pp. 956-962, PMID 21506914 .
- P. Harmatz: Enzyme replacement therapy with galsulfase for mucopolysaccharidosis VI: clinical facts and figures. In: The Turkish journal of pediatrics. Volume 52, Number 5, 2010 Sep-Oct, pp. 443-449, PMID 21434527 . (Review).
- S. Bhattacharyya, K. Kotlo et al. a .: Arylsulfatase B regulates interaction of chondroitin-4-sulfate and kininogen in renal epithelial cells. In: Biochimica et biophysica acta . Volume 1802, number 5, May 2010, pp. 472-477, doi: 10.1016 / j.bbadis.2010.01.014 . PMID 20152898 .
Individual evidence
- ↑ EC 3.1.6.12
- ↑ a b UniProt P15848
- ↑ Type VI: Enzyme Replacement Therapy (EET) viewed on January 9, 2009
- ↑ M. Beck: Galsulfase: Enzyme Replacement Therapy for Mucopolysaccharidosis Type VI (Maroteaux Lamy). In: Therapy 3, 2006, pp. 9-17.
- ↑ multiple sulfatase deficiency. In: Online Mendelian Inheritance in Man . (English)
- ↑ S. Bhattacharyya, K. Solakyildirim et al. a .: Chloroquine reduces arylsulphatase B activity and increases chondroitin-4-sulphate: implications for mechanisms of action and resistance. In: Malaria Journal . Volume 8, 2009, p. 303, doi: 10.1186 / 1475-2875-8-303 . PMID 20017940 . PMC 2805689 (free full text).
- ↑ S. Bhattacharyya, K. Solakyildirim et al. a .: Cell-bound IL-8 increases in bronchial epithelial cells after arylsulfatase B silencing due to sequestration with chondroitin-4-sulfate. In: American journal of respiratory cell and molecular biology. Volume 42, Number 1, January 2010, pp. 51-61, doi: 10.1165 / rcmb.2008-0482OC . PMID 19346317 .
- ↑ S. Bhattacharyya, JK Tobacman: Arylsulfatase B regulates colonic epithelial cell migration by effects on MMP9 expression and RhoA activation. In: Clinical & experimental metastasis. Volume 26, Number 6, 2009, pp. 535-545, doi: 10.1007 / s10585-009-9253-z . PMID 19306108 .