title: Structure of the adenylation domain of an NAD+-dependent DNA ligase.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South ParksRoad, Oxford OX1 3RE, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Singleton
authors.forename: K
authors.initials: K
authors.lastname: Håkansson
authors.forename: D J
authors.initials: DJ
authors.lastname: Timson
authors.forename: D B
authors.initials: DB
authors.lastname: Wigley
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D011088:DNA Ligases / Q000737:chemistry* / Q000378:metabolism*; D001411:Geobacillus stearothermophilus / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D011994:Recombinant Proteins; D009243:NAD; D000255:Adenosine Triphosphate; D011088:DNA Ligases