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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1ljl

E.C. nameprotein-tyrosine-phosphatase
SpeciesStaphylococcus aureus (Bacteria)
E.C. Number (IntEnz) 3.1.3.48
CSA Homologues of 1ljl
CSA Entries With UniProtID P0A006
CSA Entries With EC Number 3.1.3.48
PDBe Entry 1ljl
PDBSum Entry 1ljl
MACiE Entry M0143

Literature Report

IntroductionArsenate reductase (ArsC) from Staphylococcus aureus catalyses the reduction of arsenate to arsenite. It participates in the arsenic detoxification system of the gram-positive bacterium. ArsC also catalyses dephosphorylation in addition to reduction, although at a reduced efficiency.
Mechansim1. Ser 17 hydrogen bonds to the thiol hydrogen of Cys 10, lowering the pKa and increasing the nucleophilicity of the thiol S atom. 2. Arg 16 polarises the substrate, making the As atom more electrophilic. 3. S atom of Cys 10 nucleophilically attacks the As of the arsenate substrate. 4. The transition state is stabilised by Asp 105 via a water molecule. 5. A hydroxyl group of arsenate is protonated by an acidic water molecule, and leaves, forming a Cys 10-HAsO3- intermediate. 6. The Cys 82 S atom nucleophilically attacks Cys 10 S atom, forming a Cys 10 - Cys 82 disulphide intermediate. Electrons from the As-S bond shuttle to the arsenic, giving the release of arsenite. 7. The Cys 89 S atom attacks Cys 82 S atom, forming a Cys 82 - Cys 89 disulphide intermediate, and breaking the Cys 10 - Cys 82 disulphide and regenerating Cys 10. 8. The Cys 89 S atom is nucleophilically attacked by an S atom of thioredoxin at the surface of ArsC. This breaks the Cys 82 - Cys 89 disulphide, and forms one between Cys 89 and thioredoxin. 9. The second S atom of thioredoxin nucleophilically attacks the first S atom of thioredoxin, breaking the Cys 89 - thioredoxin disulphide, and forming reduced thioredoxin.
Reaction

Catalytic Sites for 1ljl

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AsnA1313macie:mainChainAmideStabilises the nucleophilic thiolate form of Cys 10.
SerA1717macie:sideChainHydrogen bonds to the thiol hydrogen of Cys 10, making the S atom of Cys 10 more nucleophilic.
SerA1717macie:mainChainAmideHydrogen bonds to the thiol hydrogen of Cys 10, making the S atom of Cys 10 more nucleophilic.
CysA8282macie:sideChainNucleophilically attacks the S atom of Cys 10, forming a disulphide bridge, breaking the As-S bond and causing the release of arsenite.
AspA105105macie:sideChainStabilises the transition state via a water molecule.
GlyA1212macie:mainChainAmideStabilises the nucleophilic thiolate form of Cys 10.
CysA8989macie:sideChainNucleophilically attacks the S atom of Cys 82, forming a disulphide between Cys 82 and Cys 89, and breaking the one between Cys 10 and Cys 82, reforming Cys 10.
CysA1010macie:sideChainNucleophilically attacks the As atom of arsenate, resulting in the loss of a water molecule.
SerA1414macie:mainChainAmideStabilises the nucleophilic thiolate form of Cys 10.
ArgA1616macie:sideChainSidechain hydrogen bonds to the thiol hydrogen of Cys 10, making the S atom of Cys 10 more nucleophilic. Backbone amide forms a similar hydrogen bond.
ArgA1616macie:mainChainAmideSidechain hydrogen bonds to the thiol hydrogen of Cys 10, making the S atom of Cys 10 more nucleophilic. Backbone amide forms a similar hydrogen bond.

Literature References

Notes:Asn 13 is also stated to be catalytic, although its function is not mentioned.
Messens J
All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.
Proc Natl Acad Sci U S A 2002 99 8506-8511
PubMed: 12072565
Evans B
Site-directed mutagenesis, kinetic, and spectroscopic studies of the P-loop residues in a low molecular weight protein tyrosine phosphatase.
Biochemistry 1996 35 13609-13617
PubMed: 8885840
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