Family details

Sulfatase family S1
Family S1 comprises the vast majority of the sulfatases. They catalyze the removal of sulfate ester groups according a hydrolytic mechanism (EC 3.1.6.-sulfuric ester hydrolases; EC 3.10.1.- sulfamidases). Family S1 sulfatases containing a unique catalytic residue, the Cα-formylglycine (FGly), which is posttranslationally generated from a conserved cysteine or serine. The posttranslational modification occurs when the polypeptide chain is still unfolded and is directed by a conserved N-terminal [C/S]XPXR motif (Schmidt et al. 1995; Miech et al. 1998). These S1 sulfatases adopt a similar fold comprising two (alpha/beta) domains, a large N-terminal domain containing the catalytic pocket and a smaller C-terminal domain. The active site encompasses the catalytic nucleophile formylglycine (Cys69, human ARSA numbering, family S1-1) and nine additional conserved residues (Lukatela et al. 1998): (i) four acidic/polar residues (Asp29, Asp30, Asp281, and Asn282) coordinating a calcium ion which binds and activates the sulfate group of the substrate (ii) five basic amino acids (Arg73, Lys123, His125, His229, and Lys302) stabilizing the formylglycine and/or binding the sulfate group.
Subfamilies (111)
S1_0 S1_1 S1_2 S1_3 S1_4 S1_5 S1_6 S1_7 S1_8 S1_9 S1_10 S1_11 S1_12 S1_13 S1_14
S1_15 S1_16 S1_17 S1_18 S1_19 S1_20 S1_21 S1_22 S1_23 S1_24 S1_25 S1_26 S1_27 S1_28 S1_29
S1_30 S1_31 S1_32 S1_33 S1_34 S1_35 S1_36 S1_37 S1_38 S1_39 S1_40 S1_41 S1_42 S1_43 S1_44
S1_45 S1_46 S1_47 S1_48 S1_49 S1_50 S1_51 S1_52 S1_53 S1_54 S1_55 S1_56 S1_57 S1_58 S1_59
S1_60 S1_61 S1_62 S1_63 S1_64 S1_65 S1_66 S1_67 S1_68 S1_69 S1_70 S1_71 S1_72 S1_73 S1_74
S1_75 S1_76 S1_77 S1_78 S1_79 S1_80 S1_81 S1_82 S1_83 S1_84 S1_85 S1_86 S1_87 S1_88 S1_89
S1_90 S1_91 S1_92 S1_93 S1_94 S1_95 S1_96 S1_97 S1_98 S1_99 S1_100 S1_101 S1_102 S1_103 S1_104
S1_105 S1_106 S1_107 S1_108 S1_109 S1_110 S1_N.C.

EC activities found in subfamilies
Subfamily EC Number(s) Description PubMed IDs

The consensus sequence logoplots of family S1 (Barbeyron et al. 2016)
Logos of conserved consensus sequences identified in the global alignment of formylglycine-dependent sulfatases (S1 family).
Logos of conserved consensus sequences were identified from 4058 aligned S1 sulfatases. The logo sequence of the catalytic site that corresponds to the PROSITE signature PS00523, is shown in A. The logo sequence of PROSITE signature PS00149 is shown in B. The two logo sequences of calcium binding are shown in C and D. A logo sequence from a conserved supplementary consensus sequences is shown in E. The numbers below the logo sequences indicate, at the first position, the corresponding position in reference sequence (AtsA, P51691). The corresponding consensus sequences in multi-alignment are shown below the logo sequences. The percentages in subscript are the percentages of sequences, where the amino acid is conserved in alignment. Catalytic amino acids and residues involved in calcium ion binding are in bold.
logoplot



Fold and active site of a S1 family representative
Fold (A) and active site (B) of the arylsulfatase AtsA from Pseudomonas aeruginosa PAO1 (PDB code: 1HDH). The fold is shown in cartoon representation. The amino acids and ligands of the active site is shown in sticks. The cations are shown as spheres. The figures were made using PyMoL (Version 1.8 Schrödinger, LLC).
fold



Favored catalytic mechanism of the S1 family sulfatases.
The numbering corresponds to the arylsulfatase AtsA from Pseudomonas aeruginosa PAO1. Upon substrate binding, the formyglycine is activated for nucleophilic attack on sulfur by Asp317. The sulfoenzyme intermediate is formed, and desulfation most likely occurs by elimination from the remaining fGly-diol hydroxyl (E2), catalyzed by His115. This figure was adapted from the following references (Boltes et al, 2001, Structure; Appel and Bertozzi, 2015, ACS Chem Biol) and prepared with Accelrys Draw 4.2.
catalytic mechanism