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Literature summary for 2.7.1.78 extracted from

  • Weinfeld, M.; Mani, R.S.; Abdou, I.; Aceytuno, R.D.; Glover, J.N.
    Tidying up loose ends: the role of polynucleotide kinase/phosphatase in DNA strand break repair (2011), Trends Biochem. Sci., 36, 262-271.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
XRCC1 mechanism underlying XRCC1-induced stimulation of PNKP, XRCC1 displaces PNKP from the reaction product, and addition of XRCC1 increases PNKP enzymatic turnover Homo sapiens
XRCC1 mechanism underlying XRCC1-induced stimulation of PNKP, XRCC1 displaces PNKP from the reaction product, and addition of XRCC1 increases PNKP enzymatic turnover. Phosphorylation of XRCC1 by CK2 stimulates the kinase and phosphatase activities of PNKP Mus musculus
XRCC4
-
Mus musculus
XRCC4
-
Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structure determination and analysis Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Mus musculus PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview ?
-
?
additional information Homo sapiens PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview. Phosphorylation-independent interaction between PNKP and XRCC1 in human cells, since a non-phosphorylated XRCC1S518A/T519A/T523A triple mutant is also bound ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-
Schizosaccharomyces pombe
-
-
-
Tequatrovirus T4
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview Mus musculus ?
-
?
additional information PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview. Phosphorylation-independent interaction between PNKP and XRCC1 in human cells, since a non-phosphorylated XRCC1S518A/T519A/T523A triple mutant is also bound Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
More PNKP is a multi-domain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains Homo sapiens
More PNKP is a multi-domain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains. The forkhead-associated domain is linked to the catalytic domain through a flexible polypeptide segment and acts to selectively bind acidic casein kinase 2-phosphorylated regions in XRCC1 and XRCC4, which are key scaffolding proteins in the repair of DNA single and double strand breaks, respectively. Two catalytic active sites are positioned on the same side of the protein Mus musculus
More PNKP is a multi-domain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains. The forkhead-associated domain is linked to the catalytic domain through a flexible polypeptide segment and acts to selectively bind acidic casein kinase 2-phosphorylated regions in XRCC1 and XRCC4, which are key scaffolding proteins in the repair of DNA single and double strand breaks, respectively. Two catalytic active sites are positioned on the same side of the protein Tequatrovirus T4

Synonyms

Synonyms Comment Organism
Pnk1
-
Schizosaccharomyces pombe
PNKP
-
Mus musculus
PNKP
-
Homo sapiens
PNKP
-
Tequatrovirus T4
polynucleotide kinase/phosphatase
-
Mus musculus
polynucleotide kinase/phosphatase
-
Homo sapiens
polynucleotide kinase/phosphatase
-
Schizosaccharomyces pombe
polynucleotide kinase/phosphatase
-
Tequatrovirus T4

Cofactor

Cofactor Comment Organism Structure
ATP
-
Schizosaccharomyces pombe
ATP the ATP binding site is defined by the Walker A (P-loop) and B motifs conserved in various kinases, as well as an Asp residue that activates the 5'-OH for attack on the ATP gamma-phosphate Tequatrovirus T4
ATP the ATP binding site is defined by the Walker A (P-loop) and B motifs conserved in various kinases, as well as an Asp396 that activates the 5'-OH for attack on the ATP gamma-phosphate Mus musculus
ATP the ATP binding site is defined by the Walker A (P-loop) and B motifs conserved in various kinases, as well as an Asp396 that activates the 5'-OH for attack on the ATP gamma-phosphate Homo sapiens

General Information

General Information Comment Organism
malfunction Pnk1 deletion in fission yeast renders cells sensitive to camptothecin Schizosaccharomyces pombe
malfunction PNKP depletion in human cells renders cells sensitive to camptothecin. A small molecule inhibitor of PNKP phosphatase activity enhances the sensitivity of cells to IR and camptothecin. Enzyme mutational defects can cause neurological disorders with various symptoms, e.g. a severe neurological autosomal recessive disease characterized by microcephaly, intractable seizures and developmental delay Homo sapiens
additional information molecular architecture of the enzyme, overview. The mammalian enzyme preferentially phosphorylates 5'-hydroxyl termini within nicked, gapped or double-strand breaks with single-stranded 3'-overhanging ends, whereas single-stranded 5'-termini or blunt double-stranded ends are phosphorylated less efficiently. The selective recognition of the larger, double-stranded DNA substrates is effected by a broad DNA recognition groove composed of two distinct positively charged surfaces. Mechanisms of single-strand break and double-strand break repairs, and of base excision repair, overview Homo sapiens
additional information molecular architecture of the enzyme, overview. The mammalian enzyme preferentially phosphorylates 5'-hydroxyl termini within nicked, gapped or DSBs with single-stranded 3' overhanging ends, whereas single-stranded 5'-termini or blunt double-stranded ends are phosphorylated less efficiently. The selective recognition of the larger, double-stranded DNA substrates is effected by a broad DNA recognition groove composed of two distinct positively charged surfaces. Mechanisms of single-strand break and double-strand break repairs, and base excision repair, overview Mus musculus
additional information molecular architecture of the enzyme, overview. The phage PNK DNA binding cleft forms a narrow channel leading to the conserved catalytic aspartic acid residue that accommodates single-stranded, but not double-stranded, substrates. Mechanisms of single-strand break and double-strand break repairs, overview Tequatrovirus T4
physiological function polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini Mus musculus
physiological function polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini Homo sapiens
physiological function polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini Schizosaccharomyces pombe
physiological function polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini Tequatrovirus T4