Structural highlights
Function
[PNKP_MOUSE] Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNK ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase.,Bernstein NK, Williams RS, Rakovszky ML, Cui D, Green R, Karimi-Busheri F, Mani RS, Galicia S, Koch CA, Cass CE, Durocher D, Weinfeld M, Glover JN Mol Cell. 2005 Mar 4;17(5):657-70. PMID:15749016[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bernstein NK, Williams RS, Rakovszky ML, Cui D, Green R, Karimi-Busheri F, Mani RS, Galicia S, Koch CA, Cass CE, Durocher D, Weinfeld M, Glover JN. The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase. Mol Cell. 2005 Mar 4;17(5):657-70. PMID:15749016 doi:10.1016/j.molcel.2005.02.012
