Structure of the adenylation domain of an NAD+-dependent DNA ligase

Martin R. Singleton, Kjell Håkansson, David Timson, Dale B. Wigley

Research output: Contribution to journalArticle

77 Citations (Scopus)

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 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+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.
Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalStructure
Volume7
Issue number1
DOIs
Publication statusPublished - 15 Jan 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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