Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate.
Publication Type:Journal Article
Source:Mol Cell, Volume 26, Issue 2, p.257-71 (2007)
Keywords:Adenine Nucleotides, Base Sequence, Catalytic Domain, Crystallography, X-Ray, DNA Breaks, Single-Stranded, DNA Ligase ATP, DNA Ligases, DNA Repair, DNA, Bacterial, Escherichia coli, Escherichia coli Proteins, Humans, Models, Molecular, Nucleic Acid Conformation, Protein Conformation, Protein Structure, Tertiary, Species Specificity
<p>NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria and essential for growth. Their distinctive substrate specificity and domain organization vis-a-vis human ATP-dependent ligases make them outstanding targets for anti-infective drug discovery. We report here the 2.3 A crystal structure of Escherichia coli LigA bound to an adenylylated nick, which captures LigA in a state poised for strand closure and reveals the basis for nick recognition. LigA envelopes the DNA within a protein clamp. Large protein domain movements and remodeling of the active site orchestrate progression through the three chemical steps of the ligation reaction. The structure inspires a strategy for inhibitor design.</p>