InterPro: IPR016059 ATP-dependent DNA ligase, conserved site

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (EC:6.5.1.1), the other NAD (EC:6.5.1.2), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [1,2].

Vertebrate cells encode three well-characterised DNA ligases (DNA ligases I, III and IV), all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme, two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine residue that is adenylated in the first step of the ligation reaction. The function of the second, less well-conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two sub-domains. Domain 1 consists of two antiparallel beta sheets flanked by alpha helices, whereas domain 2 consists of a five-stranded beta barrel and a single alpha helix, which form the oligonucleotide-binding fold [3, 4].