ATP-dependent polynucleotide ligases catalyze phosphodiester bond formation using nicked nucleic acid substrates with the high energy nucleotide of ATP as a cofactor in a three step reaction mechanism. DNA ligases play a vital role in the diverse processes of DNA replication, recombination and repair. ATP-dependent ligases are present in many organisms such as viruses, bacteriophages, eukarya, archaea and bacteria. Some organisms express a variety of different ligases which appear to be targeted to specific functions. ATP-dependent DNA ligases have a highly modular architecture consisting of a unique arrangement of two or more discrete domains including a DNA-binding domain, an adenylation (nucleotidyltransferase (NTase)) domain, and an oligonucleotide/oligosaccharide binding (OB)-fold domain. The adenylation domain binds ATP and contains many of the active-site residues. The adenylation and C-terminal OB-fold domains comprise a catalytic core unit that is common to most members of the ATP-dependent DNA ligase family. The catalytic core unit contains six conserved sequence motifs (I, III, IIIa, IV, V and VI) that define this family of related nucleotidyltransferases.
Comment:Sealing a nick in DNA requires three catalytic steps: first, enzyme adenylation is accomplished using ATP resulting in an AMP-linkage to the enzyme; second, the AMP is transferred to the 5' phosphate at the site of a nick; and third, phosphoryl transfer and sealing the nicked DNA.
Structure:1X9N_A; Human DNA Ligase I adenylation domain binds 5'-adenylated nicked DNA and AMP; contacts at 4A.
Jiyao W et al.(2023). "The conserved domain database in 2023.",