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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1hdh

E.C. namearylsulfatase
SpeciesPseudomonas aeruginosa (Bacteria)
E.C. Number (IntEnz) 3.1.6.1
CSA Homologues of 1hdhThere are 10 Homologs
CSA Entries With UniProtID P51691
CSA Entries With EC Number 3.1.6.1
PDBe Entry 1hdh
PDBSum Entry 1hdh
MACiE Entry 1hdh

Literature Report

IntroductionSulfatase enzymes are a highly homologous enzyme family which catalyse the hydrolysis of sulphate-ester bonds.
MechansimThe 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.
Reaction

Catalytic Sites for 1hdh

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
DdzA5151macie:ptmModified 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.
LysA375375macie:sideChainStabilises the transition state, and may act as a base depending on the pH conditions.
HisA211211macie:sideChainStabilises the transition state and may act as a base depending on the pH conditions.
LysA113113macie:sideChainContributes to electron density withdrawal on substrate to increase electrophilicity of sulphur atom.
AspA317317macie:sideChainIncreases the nucleophilicity of the aldehyde hydrate attacking oxygen by proton abstraction.
ArgA5555macie:sideChainActivates aldehyde for hydration.
HisA115115macie:sideChainActivates aldehyde for hydration.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysB375375macie:sideChainStabilises the transition state, and may act as a base depending on the pH conditions.
LysB113113macie:sideChainContributes to electron density withdrawal on substrate to increase electrophilicity of sulphur atom.
HisB211211macie:sideChainStabilises the transition state and may act as a base depending on the pH conditions.
AspB317317macie:sideChainIncreases the nucleophilicity of the aldehyde hydrate attacking oxygen by proton abstraction.
HisB115115macie:sideChainActivates aldehyde for hydration.
ArgB5555macie:sideChainActivates aldehyde for hydration.

Literature References

Notes:
Boltes I
1.3 A structure of arylsulfatase from Pseudomonas aeruginosa establishes the catalytic mechanism of sulfate ester cleavage in the sulfatase family.
Structure 2001 9 483-491
PubMed: 11435113
Waldow A
Amino acid residues forming the active site of arylsulfatase A. Role in catalytic activity and substrate binding.
J Biol Chem 1999 274 12284-12288
PubMed: 10212197
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