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Literature summary extracted from

  • Freschauf, G.K.; Mani, R.S.; Mereniuk, T.R.; Fanta, M.; Virgen, C.A.; Dianov, G.L.; Grassot, J.M.; Hall, D.G.; Weinfeld, M.
    Mechanism of action of an imido-piperidine inhibitor of human polynucleotide kinase/phosphatase (2010), J. Biol. Chem., 285, 2351-2360.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.78 the PNKP mutants are subcloned into the vector pET16b for expression in Escherichia coli BL21DE3 pLysS cells Homo sapiens
3.1.3.32 expression of wild-type and mutant enzymes in Escherichia coli strain DE3(BL21) pLysS Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.78 W331F single mutant, 90% phosphatase activity Homo sapiens
2.7.1.78 W402F single mutant, 85% phosphatase activity Homo sapiens
2.7.1.78 WFX402 mutant, all tryptophans except 402 are replaced by phenylalanine, 85% phosphatase activity Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.1.78 2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione A12B4C3, noncompetitive inhibition Homo sapiens
3.1.3.32 2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione i.e. A12B4C3, a potent, noncompetitive inhibitor of the phosphatase activity of human polynucleotide kinase/phosphatase in vitro. The inhibitor can form a ternary complex with PNKP and a DNA substrate, the inhibitor does not prevent DNA from binding to the phosphatase DNA binding site, but disrupts the secondary structure of PNKP, interaction between Trp402 of PNKP and the inhibitor. A12B4C3 sensitizes A549 human lung cancer cells to the topoisomerase I poison, camptothecin, but not the topoisomerase II poison, etoposide, in a manner similar to small interferingRNAagainst PNKP Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.78 ATP + 5'-dephospho-DNA Homo sapiens
-
 ADP + 5'-phospho-DNA
-
 r

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.78 Homo sapiens Q96T60
-
-
3.1.3.32 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.1.78 the mutant proteins are purified using ProBond resin Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.78 A-549 cell
-
 Homo sapiens
-
3.1.3.32 A-549 cell
-
 Homo sapiens
-
3.1.3.32 MDA-MB-231 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.78 ATP + 5'-dephospho-DNA
-
 Homo sapiens ADP + 5'-phospho-DNA
-
 r

Synonyms

EC Number Synonyms Comment Organism
2.7.1.78 PNKP
-
 Homo sapiens
2.7.1.78 polynucleotide kinase/phosphatase
-
 Homo sapiens
3.1.3.32 PNKP
-
 Homo sapiens
3.1.3.32 polynucleotide kinase/phosphatase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.1.78 37
-
 inhibition assay Homo sapiens
3.1.3.32 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.1.78 7.4
-
 inhibition assay Homo sapiens
3.1.3.32 7.4
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.78 ATP
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.7.1.78 additional information
-
 additional information effect of A12B4C3 binding on the W331F mutant, 95% inhibition Homo sapiens
2.7.1.78 additional information
-
 additional information effect of A12B4C3 binding on the W402F mutant, 6% inhibition Homo sapiens
2.7.1.78 additional information
-
 additional information effect of A12B4C3 binding on the WFX402 mutant, 90% inhibition Homo sapiens
2.7.1.78 additional information
-
 additional information effect of A12B4C3 binding on the wild-type PNKP, 100% inhibition Homo sapiens

General Information

EC Number General Information Comment Organism
3.1.3.32 physiological function the enzyme is involved in repair of DNA single and double strand breaks following exposure of cells to ionizing radiation Homo sapiens