1fsu: Difference between revisions
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==Overview== | ==Overview== | ||
BACKGROUND:. Sulfatases catalyze the hydrolysis of sulfuric acid esters, from a wide variety of substrates including glycosaminoglycans, glycolipids and steroids. There is sufficient common sequence similarity, within the class of sulfatase enzymes to indicate that they have a common, structure. Deficiencies of specific lysosomal sulfatases that are involved, in the degradation of glycosamino-glycans lead to rare inherited clinical, disorders termed mucopolysaccharidoses. In sufferers of multiple sulfatase, deficiency, all sulfatases are inactive because an essential, post-translational modification of a specific active-site cysteine residue, to oxo-alanine does not occur. Studies of this disorder have contributed, to location and characterization of the sulfatase active site. To, ... | BACKGROUND:. Sulfatases catalyze the hydrolysis of sulfuric acid esters, from a wide variety of substrates including glycosaminoglycans, glycolipids and steroids. There is sufficient common sequence similarity, within the class of sulfatase enzymes to indicate that they have a common, structure. Deficiencies of specific lysosomal sulfatases that are involved, in the degradation of glycosamino-glycans lead to rare inherited clinical, disorders termed mucopolysaccharidoses. In sufferers of multiple sulfatase, deficiency, all sulfatases are inactive because an essential, post-translational modification of a specific active-site cysteine residue, to oxo-alanine does not occur. Studies of this disorder have contributed, to location and characterization of the sulfatase active site. To, understand the catalytic mechanism of sulfatases, and ultimately the, determinants of their substrate specificities, we have determined the, structure of N-acetylgalactosamine-4-sulfatase. RESULTS:. The crystal, structure of the enzyme has been solved and refined at 2.5 resolution, using data recorded at both 123K and 273K. The structure has two domains, the larger of which belongs to the alpha/beta class of proteins and, contains the active site. The enzyme active site in the crystals contains, several hitherto undescribed features. The active-site cysteine residue, Cys91, is found as the sulfate derivative of the aldehyde species, oxo-alanine. The sulfate is bound to a previously undetected metal ion, which we have identified as calcium. The structure of a vanadate-inhibited, form of the enzyme has also been solved, and this structure shows that, vanadate has replaced sulfate in the active site and that the vanadate is, covalently linked to the protein. Preliminary data is presented for, crystals soaked in the monosaccharide N-acetylgalactosamine, the structure, of which forms a product complex of the enzyme. CONCLUSIONS:. The, structure of N-acetylgalactosamine-4-sulfatase reveals that residues, conserved amongst the sulfatase family are involved in stabilizing the, calcium ion and the sulfate ester in the active site. This suggests an, archetypal fold for the family of sulfatases. A catalytic role is proposed, for the post-translationally modified highly conserved cysteine residue., Despite a lack of any previously detectable sequence similarity to any, protein of known structure, the large sulfatase domain that contains the, active site closely resembles that of alkaline phosphatase: the calcium, ion in sulfatase superposes on one of the zinc ions in alkaline, phosphatase and the sulfate ester of Cys91 superposes on the phosphate ion, found in the active site of alkaline phosphatase. | ||
==About this Structure== | ==About this Structure== | ||
1FSU is a | 1FSU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N-acetylgalactosamine-4-sulfatase N-acetylgalactosamine-4-sulfatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.6.12 3.1.6.12] Structure known Active Sites: MEB and SAL. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FSU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: sulfatase]] | [[Category: sulfatase]] | ||
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Revision as of 15:27, 5 November 2007
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4-SULFATASE (HUMAN)
OverviewOverview
BACKGROUND:. Sulfatases catalyze the hydrolysis of sulfuric acid esters, from a wide variety of substrates including glycosaminoglycans, glycolipids and steroids. There is sufficient common sequence similarity, within the class of sulfatase enzymes to indicate that they have a common, structure. Deficiencies of specific lysosomal sulfatases that are involved, in the degradation of glycosamino-glycans lead to rare inherited clinical, disorders termed mucopolysaccharidoses. In sufferers of multiple sulfatase, deficiency, all sulfatases are inactive because an essential, post-translational modification of a specific active-site cysteine residue, to oxo-alanine does not occur. Studies of this disorder have contributed, to location and characterization of the sulfatase active site. To, understand the catalytic mechanism of sulfatases, and ultimately the, determinants of their substrate specificities, we have determined the, structure of N-acetylgalactosamine-4-sulfatase. RESULTS:. The crystal, structure of the enzyme has been solved and refined at 2.5 resolution, using data recorded at both 123K and 273K. The structure has two domains, the larger of which belongs to the alpha/beta class of proteins and, contains the active site. The enzyme active site in the crystals contains, several hitherto undescribed features. The active-site cysteine residue, Cys91, is found as the sulfate derivative of the aldehyde species, oxo-alanine. The sulfate is bound to a previously undetected metal ion, which we have identified as calcium. The structure of a vanadate-inhibited, form of the enzyme has also been solved, and this structure shows that, vanadate has replaced sulfate in the active site and that the vanadate is, covalently linked to the protein. Preliminary data is presented for, crystals soaked in the monosaccharide N-acetylgalactosamine, the structure, of which forms a product complex of the enzyme. CONCLUSIONS:. The, structure of N-acetylgalactosamine-4-sulfatase reveals that residues, conserved amongst the sulfatase family are involved in stabilizing the, calcium ion and the sulfate ester in the active site. This suggests an, archetypal fold for the family of sulfatases. A catalytic role is proposed, for the post-translationally modified highly conserved cysteine residue., Despite a lack of any previously detectable sequence similarity to any, protein of known structure, the large sulfatase domain that contains the, active site closely resembles that of alkaline phosphatase: the calcium, ion in sulfatase superposes on one of the zinc ions in alkaline, phosphatase and the sulfate ester of Cys91 superposes on the phosphate ion, found in the active site of alkaline phosphatase.
About this StructureAbout this Structure
1FSU is a Single protein structure of sequence from Homo sapiens with CA and CL as ligands. Active as N-acetylgalactosamine-4-sulfatase, with EC number 3.1.6.12 Structure known Active Sites: MEB and SAL. Full crystallographic information is available from OCA.
ReferenceReference
Structure of a human lysosomal sulfatase., Bond CS, Clements PR, Ashby SJ, Collyer CA, Harrop SJ, Hopwood JJ, Guss JM, Structure. 1997 Feb 15;5(2):277-89. PMID:9032078
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