The Molecular Architecture of the Mammalian DNA Repair Enzyme, Polynucleotide Kinase
Copyright policy )The Molecular Architecture of the Mammalian DNA Repair Enzyme, Polynucleotide Kinase
Mammalian polynucleotide kinase (PNK) is a key component of both the base excision repair (BER) and nonhomologous end-joining (NHEJ) DNA repair pathways. PNK acts as a 5'-kinase/3'-phosphatase to create 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for ligation during repair. PNK is recruited to repair complexes through interactions between its N-terminal FHA domain and phosphorylated components of either pathway. Here, we describe the crystal structure of intact mammalian PNK and a structure of the PNK FHA bound to a cognate phosphopeptide. The kinase domain has a broad substrate binding pocket, which preferentially recognizes double-stranded substrates with recessed 5' termini. In contrast, the phosphatase domain efficiently dephosphorylates single-stranded 3'-phospho termini as well as double-stranded substrates. The FHA domain is linked to the kinase/phosphatase catalytic domain by a flexible tether, and it exhibits a mode of target selection based on electrostatic complementarity between the binding surface and the phosphothreonine peptide.
- Mount Sinai Health System United States
- Princess Margaret Cancer Centre Canada
- University of Toronto Canada
- Cross Cancer Institute Canada
- Mount Sinai Hospital Canada
Models, Molecular, Binding Sites, DNA, Complementary, Polynucleotide 5'-Hydroxyl-Kinase, DNA Repair, Dose-Response Relationship, Drug, Amino Acid Motifs, Molecular Sequence Data, Oligonucleotides, Cell Biology, Crystallography, X-Ray, Phosphoric Monoester Hydrolases, Kinetics, Mice, Catalytic Domain, Animals, Amino Acid Sequence, Cloning, Molecular, Phosphorylation, Molecular Biology, Glutathione Transferase, Protein Binding
Models, Molecular, Binding Sites, DNA, Complementary, Polynucleotide 5'-Hydroxyl-Kinase, DNA Repair, Dose-Response Relationship, Drug, Amino Acid Motifs, Molecular Sequence Data, Oligonucleotides, Cell Biology, Crystallography, X-Ray, Phosphoric Monoester Hydrolases, Kinetics, Mice, Catalytic Domain, Animals, Amino Acid Sequence, Cloning, Molecular, Phosphorylation, Molecular Biology, Glutathione Transferase, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).191 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!