3JSN

Crystal structure of the adenylation domain of NAD+-dependent DNA ligase from Staphylococcus aureus

Summary for 3JSN

• Entry DOI: 10.2210/pdb3jsn/pdb
• Related: 3JSL
• Descriptor: DNA ligase (2 entities in total)
• Functional Keywords: nad+-dependent dna ligase, adenylation domain, staphylococcus aureus, dna damage, dna repair, dna replication, ligase, magnesium, manganese, metal-binding, nad, zinc
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 36724.79

Authors

Han, S.,Chang, J.S.,Griffor, M. (deposition date: 2009-09-10, release date: 2009-12-15, Last modification date: 2024-02-21)

Primary citation

Han, S.,Chang, J.S.,Griffor, M.
Structure of the adenylation domain of NAD(+)-dependent DNA ligase from Staphylococcus aureus.
Acta Crystallogr.,Sect.F, 65:1078-1082, 2009

PubMed Abstract: 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.

PubMed: 19923722
DOI: 10.1107/S1744309109036872

Experimental method

X-RAY DIFFRACTION (1.9 Å)