title: Biochemical and Structural Characterisation of DNA Ligases from Bacteria and Archaea.
abstract: DNA ligases are enzymes that seal breaks in the backbones of DNA, leading to them being essential for the survival of all organisms. DNA ligases have been studied from many different types of cells and organisms and shown to have diverse sizes and sequences, with well conserved specific sequences that are required for enzymatic activity. A significant number of DNA ligases have been isolated or prepared in recombinant forms and, here, we review their biochemical and structural characterisation. All DNA ligases contain an essential lysine that transfers an adenylate group from a co-factor to the 5'-phosphate of the DNA end that will ultimately be joined to the 3'-hydroxyl of the neighbouring DNA strand. The essential DNA ligases in bacteria use nicotinamide adenine dinucleotide ( β -NAD+) as their co-factor whereas those that are essential in other cells use adenosine-5'-triphosphate (ATP) as their co-factor. This observation suggests that the essential bacterial enzyme could be targeted by novel antibiotics and the complex molecular structure of β -NAD+affords multiple opportunities for chemical modification. Several recent studies have synthesised novel derivatives and their biological activity against a range of DNA ligases has been evaluated as inhibitors for drug discovery and/or non-natural substrates for biochemical applications. Here, we review the recent advances that herald new opportunities to alter the biochemical activities of these important enzymes. The recent development of modified derivatives of nucleotides highlights that the continued combination of structural, biochemical and biophysical techniques will be useful in targeting these essential cellular enzymes.
authors: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, N/A, United Kingdom.
authors: Giulia
authors: G
authors: Pergolizzi
authors: Department of Chemistry, King's College London, Faculty of Natural & Mathematical Sciences, Britannia House, 7 Trinity Street, London, N/A, United Kingdom.
authors: Gerd K
authors: GK
authors: Wagner
authors: School of Biological Sciences, University of East Anglia, Norwich, N/A, NR4 7TJ, United Kingdom r.bowater@uea.ac.uk.
authors: Richard Peter
authors: RP
authors: Bowater
keywords: ATP; Adenylate; DNA ligase; antibacterial compounds; enzyme inhibitors; β-NAD+