1YJM

Crystal structure of the FHA domain of mouse polynucleotide kinase in complex with an XRCC4-derived phosphopeptide.

Summary for 1YJM

• Entry DOI: 10.2210/pdb1yjm/pdb
• Related: 1YJ5
• Descriptor: Polynucleotide 5'-hydroxyl-kinase, 12-mer peptide from DNA-repair protein XRCC4 (3 entities in total)
• Functional Keywords: polynucleotide kinase, fha domain, xrcc4 phosphopeptide, transferase-dna binding protein complex, transferase/dna binding protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Nucleus (By similarity): Q9JLV6
• Total number of polymer chains: 6
• Total formula weight: 40100.85

Authors

Bernstein, N.K.,Williams, R.S.,Rakovszky, M.L.,Cui, D.,Green, R.,Karimi-Busheri, F.,Mani, R.S.,Galicia, S.,Koch, C.A.,Cass, C.E.,Durocher, D.,Weinfeld, M.,Glover, J.N.M. (deposition date: 2005-01-14, release date: 2005-03-15, Last modification date: 2024-10-16)

Primary citation

Bernstein, N.K.,Williams, R.S.,Rakovszky, M.L.,Cui, D.,Green, R.,Karimi-Busheri, F.,Mani, R.S.,Galicia, S.,Koch, C.A.,Cass, C.E.,Durocher, D.,Weinfeld, M.,Glover, J.N.
The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase.
Mol.Cell, 17:657-670, 2005

PubMed Abstract: 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.

PubMed: 15749016
DOI: 10.1016/j.molcel.2005.02.012

Experimental method

X-RAY DIFFRACTION (2.2 Å)