Open AccessStructure of the adenylation domain of NAD + ‐dependent DNA ligase from Staphylococcus aureus
Author(s) -
Han Seungil,
Chang Jeanne S.,
Griffor Matt
Publication year - 2009
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309109036872
Subject(s) - dna ligase , dna ligases , phosphodiester bond , dna , nad+ kinase , dna replication , biochemistry , biology , dna repair , dna clamp , ubiquitin ligase , chemistry , enzyme , ubiquitin , rna , reverse transcriptase , gene
DNA ligase catalyzes phosphodiester‐bond formation between immediately adjacent 5′‐phosphate and 3′‐hydroxyl groups in double‐stranded DNA and plays a central role in many cellular and biochemical processes, including DNA replication, repair and recombination. Bacterial NAD + ‐dependent DNA ligases have been extensively characterized as potential antibacterial targets because of their essentiality and their structural distinction from human ATP‐dependent DNA ligases. The high‐resolution structure of the adenylation domain of Staphylococcus aureus NAD + ‐dependent DNA ligase establishes the conserved domain architecture with other bacterial adenylation domains. Two apo crystal structures revealed that the active site possesses the preformed NAD + ‐binding pocket and the `C2 tunnel' lined with hydrophobic residues: Leu80, Phe224, Leu287, Phe295 and Trp302. The C2 tunnel is unique to bacterial DNA ligases and the Leu80 side chain at the mouth of the tunnel points inside the tunnel and forms a narrow funnel in the S. aureus DNA ligase structure. Taken together with other DNA ligase structures, the S. aureus DNA ligase structure provides a basis for a more integrated understanding of substrate recognition and catalysis and will be also be of help in the development of small‐molecule inhibitors.