3u7e | pdb_00003u7e
Crystal structure of mPNKP catalytic fragment (D170A)
Structural highlights
FunctionPNKP_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. Publication Abstract from PubMedPolynucleotide kinase/phosphatase (PNKP) is a critical mammalian DNA repair enzyme that generates 5'-phosphate and 3'-hydroxyl groups at damaged DNA termini that are required for subsequent processing by DNA ligases and polymerases. The PNKP phosphatase domain recognizes 3'-phosphate termini within DNA nicks, gaps, or at double- or single-strand breaks. Here we present a mechanistic rationale for the recognition of damaged DNA termini by the PNKP phosphatase domain. The crystal structures of PNKP bound to single-stranded DNA substrates reveals a narrow active site cleft that accommodates a single-stranded substrate in a sequence-independent manner. Biochemical studies suggest that the terminal base pairs of double-stranded substrates near the 3'-phosphate are destabilized by PNKP to allow substrate access to the active site. A positively charged surface distinct from the active site specifically facilitates interactions with double-stranded substrates, providing a complex DNA binding surface that enables the recognition of diverse substrates. Structural basis for the phosphatase activity of polynucleotide kinase/phosphatase on single- and double-stranded DNA substrates.,Coquelle N, Havali-Shahriari Z, Bernstein N, Green R, Glover JN Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21022-7. Epub 2011 Dec 14. PMID:22171004[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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