Publications

• 1.3 A structure of arylsulfatase from Pseudomonas aeruginosa establishes the catalytic mechanism of sulfate ester cleavage in the sulfatase family.

  Boltes I., Czapinska H., Kahnert A., von Buelow R., Dierks T., Schmidt B., von Figura K., Kertesz M.A., Uson I.

  <h4>Background</h4>Sulfatases constitute a family of enzymes with a highly conserved active site region including a Calpha-formylglycine that is posttranslationally generated by the oxidation of a conserved cysteine or serine residue. The crystal structures of two human arylsulfatases, ASA and ASB ... >> More

  <h4>Background</h4>Sulfatases constitute a family of enzymes with a highly conserved active site region including a Calpha-formylglycine that is posttranslationally generated by the oxidation of a conserved cysteine or serine residue. The crystal structures of two human arylsulfatases, ASA and ASB, along with ASA mutants and their complexes led to different proposals for the catalytic mechanism in the hydrolysis of sulfate esters.<h4>Results</h4>The crystal structure of a bacterial sulfatase from Pseudomonas aeruginosa (PAS) has been determined at 1.3 A. Fold and active site region are strikingly similar to those of the known human sulfatases. The structure allows a precise determination of the active site region, unequivocally showing the presence of a Calpha-formylglycine hydrate as the key catalytic residue. Furthermore, the cation located in the active site is unambiguously characterized as calcium by both its B value and the geometry of its coordination sphere. The active site contains a noncovalently bonded sulfate that occupies the same position as the one in para-nitrocatecholsulfate in previously studied ASA complexes.<h4>Conclusions</h4>The structure of PAS shows that the resting state of the key catalytic residue in sulfatases is a formylglycine hydrate. These structural data establish a mechanism for sulfate ester cleavage involving an aldehyde hydrate as the functional group that initiates the reaction through a nucleophilic attack on the sulfur atom in the substrate. The alcohol is eliminated from a reaction intermediate containing pentacoordinated sulfur. Subsequent elimination of the sulfate regenerates the aldehyde, which is again hydrated. The metal cation involved in stabilizing the charge and anchoring the substrate during catalysis is established as calcium. << Less

  Structure 9:483-491(2001) [PubMed] [EuropePMC]

• Studies on sulphatases. 13. The hydrolysis of substituted phenyl sulphates by the arylsulphatase of Alcaligenes metalcaligenes.

  DODGSON K.S., SPENCER B., WILLIAMS K.

  Biochem J 64:216-221(1956) [PubMed] [EuropePMC]

• A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency.

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

  Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder characterized by a decreased activity of all known sulfatases. The deficiency of sulfatases was proposed to result from the lack of a co- or posttranslational modification that is common to all sulfatases and required for their ca ... >> More

  Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder characterized by a decreased activity of all known sulfatases. The deficiency of sulfatases was proposed to result from the lack of a co- or posttranslational modification that is common to all sulfatases and required for their catalytic activity. Structural analysis of two catalytically active sulfatases revealed that a cysteine residue that is predicted from the cDNA sequence and conserved among all known sulfatases is replaced by a 2-amino-3-oxopropionic acid residue, while in sulfatases derived from MSD cells, this cysteine residue is retained. It is proposed that the co- or posttranslational conversion of a cysteine to 2-amino-3-oxopropionic acid is required for generating catalytically active sulfatases and that deficiency of this protein modification is the cause of MSD. << Less

  Cell 82:271-278(1995) [PubMed] [EuropePMC]

• Sulphatases, lysosomes and disease.

  Roy A.B.

  Aust J Exp Biol Med Sci 54:111-135(1976) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• The activation of an arysulphatase from ox liver by chloride and other anions.

  WEBB E.C., MORROW P.F.

  Biochem J 73:7-15(1959) [PubMed] [EuropePMC]

• Posttranslational formation of formylglycine in prokaryotic sulfatases by modification of either cysteine or serine.

  Dierks T., Miech C., Hummerjohann J., Schmidt B., Kertesz M.A., von Figura K.

  Eukaryotic sulfatases carry an alpha-formylglycine residue that is essential for activity and is located within the catalytic site. This formylglycine is generated by posttranslational modification of a conserved cysteine residue. The arylsulfatase gene of Pseudomonas aeruginosa also encodes a cys ... >> More

  Eukaryotic sulfatases carry an alpha-formylglycine residue that is essential for activity and is located within the catalytic site. This formylglycine is generated by posttranslational modification of a conserved cysteine residue. The arylsulfatase gene of Pseudomonas aeruginosa also encodes a cysteine at the critical position. This protein could be expressed in active form in a sulfatase-deficient strain of P. aeruginosa, thereby restoring growth on aromatic sulfates as sole sulfur source, and in Escherichia coli. Analysis of the mature protein expressed in E. coli revealed the presence of formylglycine at the expected position, showing that the cysteine is also converted to formylglycine in a prokaryotic sulfatase. Substituting the relevant cysteine by a serine codon in the P. aeruginosa gene led to expression of inactive sulfatase protein, lacking the formylglycine. The machinery catalyzing the modification of the Pseudomonas sulfatase in E. coli therefore resembles the eukaryotic machinery, accepting cysteine but not serine as a modification substrate. By contrast, in the arylsulfatase of Klebsiella pneumoniae a formylglycine is found generated by modification of a serine residue. The expression of both the Klebsiella and the Pseudomonas sulfatases as active enzymes in E. coli suggests that two modification systems are present, or that a common modification system is modulated by a cofactor. << Less

  J. Biol. Chem. 273:25560-25564(1998) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• The synthesis and hydrolysis of sulfate esters.

  ROY A.B.

  Adv Enzymol Relat Subj Biochem 22:205-235(1960) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.