DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalyzing 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 ).
This entry represents the N-terminal region of NAD-dependent bacterial DNA ligases. They are proteins of about 75 to 85 Kd whose sequence is well conserved [ (PUBMED:1526462) (PUBMED:8390989) ]. They also show similarity to yicF, an Escherichia coli hypothetical protein of 63 Kd. The region described by this model covers the adenylation, OB-fold and zinc-finger domains of these enzymes [ (PUBMED:10698952) (PUBMED:10368271) ].
Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications.
EMBO J. 2000; 19: 1119-29
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DNA ligases catalyze the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor. Despite the difference in cofactor specificity and limited overall sequence similarity, the two classes of DNA ligase share basically the same catalytic mechanism. In this study, the crystal structure of an NAD(+)-dependent DNA ligase from Thermus filiformis, a 667 residue multidomain protein, has been determined by the multiwavelength anomalous diffraction (MAD) method. It reveals highly modular architecture and a unique circular arrangement of its four distinct domains. It also provides clues for protein flexibility and DNA-binding sites. A model for the multidomain ligase action involving large conformational changes is proposed.
Structure of the adenylation domain of an NAD+-dependent DNA ligase.
Structure Fold Des. 1999; 7: 35-42
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BACKGROUND: DNA ligases catalyse phosphodiester bond formation between adjacent bases in nicked DNA, thereby sealing the nick. A key step in the catalytic mechanism is the formation of an adenylated DNA intermediate. The adenyl group is derived from either ATP (in eucaryotes and archaea) or NAD+4 (in bacteria). This difference in cofactor specificity suggests that DNA ligase may be a useful antibiotic target. RESULTS: The crystal structure of the adenylation domain of the NAD+-dependent DNA ligase from Bacillus stearothermophilus has been determined at 2.8 A resolution. Despite a complete lack of detectable sequence similarity, the fold of the central core of this domain shares homology with the equivalent region of ATP-dependent DNA ligases, providing strong evidence for the location of the NAD+-binding site. CONCLUSIONS: Comparison of the structure of the NAD+4-dependent DNA ligase with that of ATP-dependent ligases and mRNA-capping enzymes demonstrates the manifold utilisation of a conserved nucleotidyltransferase domain within this family of enzymes. Whilst this conserved core domain retains a common mode of nucleotide binding and activation, it is the additional domains at the N terminus and/or the C terminus that provide the alternative specificities and functionalities in the different members of this enzyme superfamily.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with LIGANc domain which could be assigned to a KEGG orthologous group, and not all proteins containing LIGANc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
