3uq8

Publication Abstract from PubMed

NAD+-dependent DNA ligases (LigA) are essential bacterial enzymes that catalyze phosphodiester bond formation during DNA replication and repair processes. Phosphodiester bond formation proceeds through a well-conserved 3-step reaction mechanism. In the first step, the LigA adenylation domain interacts with NAD+ to form a covalent enzyme-AMP. Although it is well-established that the specificity for binding of NAD+ resides within the adenylation domain, the precise recognition elements for the initial binding event remain unclear. We report here the structure of the adenylation domain from Haemophilus influenzae LigA. This structure is a first snapshot of a LigA-AMP intermediate with NAD+ bound to domain 1a in its open conformation. The binding affinities of NAD+ for adenylated and non-adenylated forms of the H. influenzae LigA adenylation domain were measured using isothermal titration calorimetry. NAD+ was only observed to bind to domain 1a and not domain 1b. The combined crystalographic and NAD+-binding data suggest that the initial recognition of NAD+ is via the NMN binding region in domain 1a of LigA.

Structure guided understanding of NAD+ recognition in bacterial DNA ligases.,Lahiri SD, Mills S, Gu RF, Gao N, Walkup G, Karantzeni I ACS Chem Biol. 2012 Jan 9. PMID:22230472^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.