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.
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: Aron Marchler-Bauer; John B Anderson; Carol DeWeese-Scott; Natalie D Fedorova; Lewis Y Geer; Siqian He; David I Hurwitz; John D Jackson; Aviva R Jacobs; Christopher J Lanczycki; Cynthia A Liebert; Chunlei Liu; Thomas Madej; Gabriele H Marchler; Raja Mazumder; Anastasia N Nikolskaya; Anna R Panchenko; Bachoti S Rao; Benjamin A Shoemaker; Vahan Simonyan; James S Song; Paul A Thiessen; Sona Vasudevan; Yanli Wang; Roxanne A Yamashita; Jodie J Yin; Stephen H Bryant Journal: Nucleic Acids Res Date: 2003-01-01 Impact factor: 16.971
Authors: F S Kaczmarek; R P Zaniewski; T D Gootz; D E Danley; M N Mansour; M Griffor; A V Kamath; M Cronan; J Mueller; D Sun; P K Martin; B Benton; L McDowell; D Biek; M B Schmid Journal: J Bacteriol Date: 2001-05 Impact factor: 3.490