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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1hdh
Original Entry
Title:
Hydrolase
Compound:
Arylsulfatase
Mutant:
No
UniProt/Swiss-Prot:
P51691-ARS_PSEAE
EC Class:
3.1.6.1
Other CSA Entries:
Overview of all sites for 1hdh
Homologues of 1hdh
Entries for UniProt/Swiss-Prot: P51691
Entries for EC: 3.1.6.1
Other Databases:
PDB entry: 1hdh
PDBsum entry: 1hdh
UniProt/Swiss-Prot: P51691
IntEnz entry: 3.1.6.1
Literature Report:
Introduction:
Sulfatase enzymes are a highly homologous enzyme family which catalyse the hydrolysis of sulphate-ester bonds.
Mechanism:
The sulfate ester cleavage involves an aldehyde hydrate, a modified residue FGly 51, as the functional group that initiates the reaction through a nucleophilic attack on the sulphur atom of the substrate. Lys 113 and FGly 51 contribute to electron density withdrawal from the sulfate oxygen atoms to give increased electrophilicity at the sulphur centre. The nucleophilicity of the oxygen in the aldehyde hydrate is enhanced by coordination to the Ca cation and facilitated proton transfer by Asp 317. An alcohol is eliminated in an SN2 substitution reaction, and the pentacoordinate sulphur intermediate is stabilised by Lys 375, His 211 and the Ca cation - the His or the Lys can act as proton donors to the alcoholate depending on the pH conditions. Sulfate elimination regenerates the aldehyde, by deprotonation of FGly 51 with His 115 acting as a proton acceptor. The aldehyde is hydrated by water, with the C-O bond being polarised by His 115, Arg 55, Asn 318 and the Ca cation.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
DDZA 51 51Sidechain
ModifiedModified
Acid/baseSubstrate
NucleophileSubstrate
Modified to an aldehyde hydrate, this is used in the nucleophilic attack of the sulphur atom. It also increases the electrophilicity of the sulphur atom of the substrate and is deprotonated in sulfate elimination.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10212197 Related protein: UniProt P15289 Conservation of residue
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism
PubMed ID 10212197 Related protein: UniProt P15289 Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ARGA 55 55Sidechain
ElectrostaticResidue
Activates aldehyde for hydration.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 113 113Sidechain
ElectrostaticSubstrate
Contributes to electron density withdrawal on substrate to increase electrophilicity of sulphur atom.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism
PubMed ID 10212197 Related protein: UniProt P15289 Mutagenesis of residue
PubMed ID 10212197 Related protein: UniProt P15289 Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 10212197 Related protein: UniProt P15289 pH dependence of reaction
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 10212197 Related protein: UniProt P15289 Conservation of residue
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 115 115Sidechain
ElectrostaticResidue
Activates aldehyde for hydration.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10212197 Related protein: UniProt P15289 Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 Mutagenesis of residue
PubMed ID 10212197 Related protein: UniProt P15289 Structural similarity to homologue of known mechanism
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 pH dependence of reaction
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 10212197 Related protein: UniProt P15289 Residue is positioned appropriately (ligand position hypothetical)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 211 211Sidechain
Acid/baseSubstrate
ElectrostaticTransition state
Stabilises the transition state and may act as a base depending on the pH conditions.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10212197 Related protein: UniProt P15289 Structural similarity to homologue of known mechanism
PubMed ID 10212197 Related protein: UniProt P15289 Mutagenesis of residue
PubMed ID 10212197 Related protein: UniProt P15289 Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 pH dependence of reaction
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 317 317Sidechain
Acid/baseResidue
Increases the nucleophilicity of the aldehyde hydrate attacking oxygen by proton abstraction.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10212197 Related protein: UniProt P15289 Structural similarity to homologue of known mechanism
PubMed ID 10212197 Related protein: UniProt P15289 Conservation of residue
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 10212197 Related protein: UniProt P15289 Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 pH dependence of reaction
PubMed ID 10212197 Related protein: UniProt P15289 Mutagenesis of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 375 375Sidechain
Acid/baseSubstrate
ElectrostaticTransition state
Stabilises the transition state, and may act as a base depending on the pH conditions.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10212197 Related protein: UniProt P15289 Conservation of residue
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism
PubMed ID 10212197 Related protein: UniProt P15289 pH dependence of reaction
PubMed ID 10212197 Related protein: UniProt P15289 Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 Mutagenesis of residue
PubMed ID 10212197 Related protein: UniProt P15289 Structural similarity to homologue of known mechanism
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
CAA1528 0Sidechain
ElectrostaticResidue
ElectrostaticTransition state
Increases the nucleophilicity of the attacking oxygen of the aldehyde hydrate by coordination, and primes the residue for hydration at the end of the catalytic cycle. Also stabilises the pentacoordinate sulphur intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11435113 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 10212197 Related protein: UniProt P15289 Ligand is essential for catalysis
PubMed ID 11435113 Current protein Conservation of residue
PubMed ID 10212197 Related protein: UniProt P15289 Structural similarity to homologue of known mechanism
PubMed ID 11435113 Current protein Structural similarity to homologue of known mechanism
PubMed ID 10212197 Related protein: UniProt P15289 Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 10212197 Related protein: UniProt P15289 Conservation of residue
References:
1
1.3 A structure of arylsulfatase from Pseudomonas aeruginosa establishes the catalytic mechanism of sulfate ester cleavage in the sulfatase family.
I. Boltes and H. Czapinska and A. Kahnert and R. von Bülow and T. Dierks and B. Schmidt and K. von Figura and M. A. Kertesz and I. Usón
Structure (Camb) 9, (6) 483-91, (2001).
11435113
2
Amino acid residues forming the active site of arylsulfatase A. Role in catalytic activity and substrate binding.
A. Waldow and B. Schmidt and T. Dierks and R. von Bülow and K. von Figura
J Biol Chem 274, (18) 12284-8, (1999).
10212197
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