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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1d5r
Original Entry
Title:
Hydrolase
Compound:
Phosphoinositide phosphotase pten
Mutant:
Yes
UniProt/Swiss-Prot:
O00633-PTEN_HUMAN
EC Class:
3.1.3.67
Other CSA Entries:
Overview of all sites for 1d5r
Homologues of 1d5r
Entries for UniProt/Swiss-Prot: O00633
Entries for EC: 3.1.3.67
Other Databases:
PDB entry: 1d5r
PDBsum entry: 1d5r
UniProt/Swiss-Prot: O00633
IntEnz entry: 3.1.3.67
Literature Report:
Introduction:
PTEN is a phosphatase and a tumour suppressor. It can act on both polypeptide and phosphoinositide substrates in vitro. PTEN can dephosphorylate tyrosine-, serine-, and threonine-phosphorylated peptides, and this activity requires highly acidic substrates. PTEN can also dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate in vitro, with specificity for the phosphate group at the D3 position of the inositol ring.
Mechanism:
The mechanism of PTEN is similar to that of Protein Tyrosine Phosphatase 1B. Cys124 functions as a nucleophile, accepting the phosphate moiety from the phosphorylated amino acid and generating a phosphocysteine intermediate. Asp92 serves as an acid to protonate the hydroxyl oxygen atom of the leaving group. Next, the phosphate moiety is transferred to a water molecule, restoring the enzyme. Arg130 stabilises the transition state.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 92 92Sidechain
Acid/baseSubstrate
It serves as an acid to protonate the hydroxyl oxygen atom of the leaving group.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10555148 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
CYSA 124 124Sidechain
NucleophileSubstrate
It acts as a nucleophile, accepting the phosphate moiety from the phosphorylated amino acid and generating a phosphocysteine intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 9593664 Current protein Mutagenesis of residue
PubMed ID 10555148 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ARGA 130 130Sidechain
ElectrostaticTransition state
It stabilises the transition state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10555148 Current protein Structural similarity to homologue of known mechanism
References:
1
PTEN mutations in gliomas and glioneuronal tumors.
E. M. Duerr and B. Rollbrocker and Y. Hayashi and N. Peters and B. Meyer-Puttlitz and D. N. Louis and J. Schramm and O. D. Wiestler and R. Parsons and C. Eng and A. von Deimling
Oncogene 16, (17) 2259-64, (1998).
9593664
2
Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
J. O. Lee and H. Yang and M. M. Georgescu and A. Di Cristofano and T. Maehama and Y. Shi and J. E. Dixon and P. Pandolfi and N. P. Pavletich
Cell 99, (3) 323-34, (1999).
10555148
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