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Literature summary for 3.1.3.67 extracted from

  • Redfern, R.E.; Redfern, D.; Furgason, M.L.; Munson, M.; Ross, A.H.; Gericke, A.
    PTEN phosphatase selectively binds phosphoinositides and undergoes structural changes (2008), Biochemistry, 47, 2162-2171.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
phosphatidylinositol 4,5-biphosphate Enhances PTEN phosphatase activity by inducing conformational change by binding to the PTEN N-terminal domain. Binding constants are in accord with enzyme kinetic measurements showing that phosphatidylinositol 4,5-bisphosphate enhances phosphatidylinositol 3,4,5-triphosphate hydrolysis more effectively than phosphatidylserine, and the binding constant of phosphatidylinositol 4,5-biphosphate of 8.14 microM is in general agreement with the phosphatidylinositol 4,5-bisphosphate concentration requires to activate the PTEN phosphatase. The magnitude of this binding constant indicates that PTEN-phosphatidylinositol 4,5-bisphosphate interactions are physiologically relevant since the effective cellular concentration of phosphatidylinositol 4,5-bisphosphate is thought to be 10 microM, and local phosphatidylinositol 4,5-bisphosphate concentrations are likely to reach even higher levels. Increasing the phosphatidylserine concentration to 25 mol results in stronger binding, but even for these higher surface charge densities, binding constant is still lower than the corresponding values for the phosphatidylcholine/phosphatidylinositol 4,5-bisphosphate vesicle system. Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
The cDNA encoding full-length 1-403 PTEN is cloned into the NdeI and XhoI sites of the pET30b vector, thereby introducing a poly-His tag at the C-terminus. Point mutations are introduced with the Quick-Change site-directed mutagenesis kit. Deletion mutant 16-403 is prepared by PCR with the Phusion DNA polymerase. PTEN proteins are expressed in Escherichia coli BL21 (DE3) cells. Homo sapiens

Protein Variants

Protein Variants Comment Organism
DELTA1-15 phosphatidylinositol 4,5-biphosphate has no effect on binding of PTEN16-403 Homo sapiens
K13E the binding of the PTEN mutant K13E, which is a tumor-derived mutation that renders PTEN inactive, is not affected by phosphatidylinositol 4,5-biphosphate Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens N-terminal domain of PTEN binds anionic lipids via nonspecific electrostatic interactions ?
-
?
additional information Homo sapiens PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor that is mutated or deleted in a variety of human tumors, and even loss of only one PTEN gene profoundly affects carcinogenesis ?
-
?
additional information Homo sapiens PTEN binds synergistically phosphatidylinositol 4,5-biphosphate and phosphatidylserine ?
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?
additional information Homo sapiens PTEN encodes a phosphatidylinositol phosphate phosphatase specific for the 3-position of the inositol ring, it influences many biological processes in both developing and adult organisms ?
-
?
phosphatidylinositol 3,4,5-triphosphate + H2O Homo sapiens
-
phosphatidylinositol 4,5-bisphosphate + phosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
Poly-His tag proteins are purified with a HisTrap HP kit using buffers with 10 mM mercaptoethanol, enzymes are further purified with a gel filtration column in 100 mM NaCl, 10 mM Tris, pH 7.4, and 1 mM dithiothreitol. Final purification is done with a anion exchange column in 10 mM Tris, pH 7.4 with a linear gradient from 50-600 mM NaCl. Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information N-terminal domain of PTEN binds anionic lipids via nonspecific electrostatic interactions Homo sapiens ?
-
?
additional information PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor that is mutated or deleted in a variety of human tumors, and even loss of only one PTEN gene profoundly affects carcinogenesis Homo sapiens ?
-
?
additional information PTEN binds synergistically phosphatidylinositol 4,5-biphosphate and phosphatidylserine Homo sapiens ?
-
?
additional information PTEN encodes a phosphatidylinositol phosphate phosphatase specific for the 3-position of the inositol ring, it influences many biological processes in both developing and adult organisms Homo sapiens ?
-
?
phosphatidylinositol 3,4,5-triphosphate + H2O
-
Homo sapiens phosphatidylinositol 4,5-bisphosphate + phosphate
-
?

Synonyms

Synonyms Comment Organism
PTEN
-
Homo sapiens
PTEN phosphatase
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Homo sapiens