FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs.
Gap Endonuclease 1 (GEN1) is a Holliday junction resolvase reported to symmetrically cleave Holliday junctions and allow religation without additional processing. GEN1 is a member of the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.
Comment:The PIN domain superfamily contains three highly conserved catalytic residues which coordinate metal ions, in some members, additional metal coordinating residues can be found. Some members of the superfamily, including MKT1, lack several of these key catalytic residues.
Comment:Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region (not included) defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.
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