DNA ligase (NAD(+)-dependent) (LigA) (LigA)

DNA ligase (LigA) from Enterococcus faecalis is an essential enzyme that catalyzes the formation of phosphodiester bonds between adjacent 3'-hydroxyl and 5'-phosphoryl termini in double-stranded DNA [1, 6]. Unlike eukaryotic DNA ligases which use ATP as a cofactor, bacterial LigA is strictly dependent on nicotinamide adenine dinucleotide (NAD+), making it a highly selective target for antibacterial drug development [2, 4]. It plays a critical role in fundamental cellular processes including DNA replication, repair, and recombination [1, 6]. Inhibition of LigA leads to the accumulation of DNA nicks and Okazaki fragments, ultimately resulting in bacterial cell death [4, 6]. Given the rise of multidrug-resistant E. faecalis strains, such as vancomycin-resistant enterococci (VRE), LigA represents a promising target for novel antibiotics [8, 20]. Experimental inhibitors like pyridochromanones and adenosine analogs have demonstrated potent activity and selectivity for the bacterial enzyme over human counterparts [2, 4]. These compounds typically act by competing with the NAD+ cofactor for binding to the enzyme's adenylation domain [4, 6]. Although no LigA inhibitors are currently approved for clinical use, they are actively being researched as potential broad-spectrum antibacterial agents [4, 11].

Other names

NAD(+)-dependent DNA ligasePolydeoxyribonucleotide synthase (NAD(+))ligADNA ligase (NAD(+))

Inhibition of NAD(+)-dependent DNA ligation by competing with the NAD(+) cofactor at the adenylation domain.