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Catalytic Site Atlas

CSA LITERATURE entry for 1hy3

E.C. nameestrone sulfotransferase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 2.8.2.4
CSA Homologues of 1hy3
CSA Entries With UniProtID P49888
CSA Entries With EC Number 2.8.2.4
PDBe Entry 1hy3
PDBSum Entry 1hy3
MACiE Entry M0154

Literature Report

IntroductionEstrogen sulfotransferase (EST) transfers the sulfate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the phenolic oxygen of estrogenic steroids. EST plays a role in many carcinogenic processes, with polymorphism implicated in genetic risk towards some cancers.
MechansimThe mechanism is SN2-like in-line displacement, with the phenolic hydroxy group acting as the nucleophile (made more nucleophilic by hydrogen bonding with His 107, which also transfers the phenolic proton to the sulfate group).
Lys 47 hydrogen bonds to the oxygen atom bridging PAPS 5' phosphate and sulfate groups. This promotes dissociation of the sulfate group from PAPS and may transfer a proton to the PAP product.
The invariant Ser 137 plays an important regulatory role. It hydrogen bonds to Lys 47 in the absence of the steroid substrate, preventing Lys 47 assisting in hydrolysis of PAPS. Once the steroid binds, the hydrogen bond is broken and the transfer reaction can take place.
Reaction

Catalytic Sites for 1hy3

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA107107macie:sideChainHis 107 activates the phenolic hydroxy group of the steroid substrate as a nucleophile. It also transfers the hydrogen bonded proton from the phenolic oxygen to the sulfate group.
LysA4747macie:sideChainLys 43 promotes dissociation of the sulfate group from PAPS and the transfer to the steroid. It also stabilises the transition state and may also donate a proton to the PAP product.
SerA137137macie:sideChainPlays an important regulatory role. Hydrogen bonds to Lys 47 in the absence of the steroid substrate, preventing Lys 47 assisting in hydrolysis of PAPS. Once the steroid binds, the hydrogen bond is broken and the transfer reaction can take place.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB107107macie:sideChainHis 107 activates the phenolic hydroxy group of the steroid substrate as a nucleophile. It also transfers the hydrogen bonded proton from the phenolic oxygen to the sulfate group.
LysB4747macie:sideChainLys 43 promotes dissociation of the sulfate group from PAPS and the transfer to the steroid. It also stabilises the transition state and may also donate a proton to the PAP product.
SerB137137macie:sideChainPlays an important regulatory role. Hydrogen bonds to Lys 47 in the absence of the steroid substrate, preventing Lys 47 assisting in hydrolysis of PAPS. Once the steroid binds, the hydrogen bond is broken and the transfer reaction can take place.

Literature References

Notes:
Pedersen LC
Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction.
J Biol Chem 2002 277 17928-17932
PubMed: 11884392
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