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+ (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 Å 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+-dependent DNA ligase with that of ATP-dependent ligases and mRNA-capping enzymes demonstrates the manifold utilization 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.
Singleton, M. R., Håkansson, K., Timson, D. J., & Wigley, D. B. (1999). Structure of the adenylation domain of an NAD+-dependent DNA ligase. Structure, 7(1), 35–42. https://doi.org/10.1016/S0969-2126(99)80007-0